Case series Archives - Neurosurgery

What is the main target region in the brain for dTMS when treating OCD?
1. A. Temporal lobe
2. B. Prefrontal cortex
3. C. Anterior cingulate cortex (ACC)
4. D. Occipital lobe

What is the proposed mechanism of action for dTMS in the treatment of OCD?
1. A. Regulating sleep patterns
2. B. Modulating brain activity in the prefrontal cortex
3. C. Enhancing sensory perception
4. D. Modulating brain activity in the ACC to reduce obsessive thoughts and compulsive behaviors

How is a typical dTMS treatment protocol for OCD structured?
1. A. One session per month
2. B. Multiple sessions administered in a single day
3. C. Multiple sessions administered over several weeks
4. D. Single session with high intensity

What are some common side effects associated with dTMS treatment for OCD?
1. A. Nausea and dizziness
2. B. Severe and long-lasting headaches
3. C. Mild discomfort or temporary headache at the stimulation site
4. D. Memory loss and visual disturbances

In terms of efficacy, what have research findings on dTMS for OCD shown?
1. A. Consistently significant benefits for all individuals
2. B. No impact on OCD symptoms
3. C. Mixed results with some individuals experiencing a reduction in symptoms
4. D. A complete cure for OCD

Why is individualized treatment evaluation important when considering dTMS as a treatment option for OCD?
1. A. To determine the color of the treatment device
2. B. To streamline the treatment process
3. C. To ensure a one-size-fits-all approach
4. D. Because the effectiveness of dTMS varies from person to person

Who conducted a study to evaluate the current research on the effectiveness of dTMS therapy for individuals with treatment-resistant OCD?
1. A. Dr. John Smith
2. B. Dr. Emily Johnson
3. C. McCathern et al.
4. D. Roth et al.

In a study by Smárason et al., what was the primary focus regarding the relationship between dTMS and OCD symptoms?
1. A. The impact of dTMS on anxiety symptoms
2. B. The relationship between dTMS and depression symptoms
3. C. The impact of dTMS on sleep patterns
4. D. The effects of dTMS on cognitive functioning

What was the conclusion of the study by Smárason et al. regarding the impact of dTMS on depression symptoms during the treatment of OCD?
1. A. dTMS significantly worsened depression symptoms
2. B. dTMS had no effect on depression symptoms
3. C. dTMS significantly improved depression symptoms
4. D. Changes in depression symptoms were unpredictable

In a case series by Ikawa et al., what was the response rate to dTMS treatment for OCD, and what were the key findings in terms of symptom improvements?
1. A. 100% response rate; no symptom improvements observed
2. B. 75% response rate; moderate symptom improvements
3. C. 53.9% response rate; significant improvements in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores
4. D. 30% response rate; slight symptom improvements

—- Answers:

C. Anterior cingulate cortex (ACC)

D. Modulating brain activity in the ACC to reduce obsessive thoughts and compulsive behaviors

C. Multiple sessions administered over several weeks

C. Mild discomfort or temporary headache at the stimulation site

C. Mixed results with some individuals experiencing a reduction in symptoms

D. Because the effectiveness of dTMS varies from person to person

C. McCathern et al.

B. The relationship between dTMS and depression symptoms

D. Changes in depression symptoms were unpredictable

C. 53.9% response rate; significant improvements in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores

Deep Transcranial Magnetic Stimulation (dTMS) has been explored as a potential treatment for Obsessive-Compulsive Disorder (OCD). OCD is a mental health condition characterized by recurrent, distressing obsessions and repetitive, often ritualistic compulsions. While conventional treatments such as cognitive-behavioral therapy and medication are effective for many individuals with OCD, some people do not respond adequately or experience significant side effects. This has led to the investigation of alternative approaches, including dTMS.

Here are some key points regarding dTMS for OCD treatment:

Targeted Brain Regions: In the context of OCD treatment, dTMS typically targets the anterior cingulate cortex (ACC), a brain region associated with the regulation of cognitive and emotional processes. Dysfunction in this area is believed to play a role in the development and persistence of OCD symptoms.

Mechanism of Action: The idea behind dTMS for OCD is to modulate brain activity in the ACC and normalize its functioning. By applying magnetic pulses to this region, the hope is to reduce obsessive thoughts and compulsive behaviors.

Treatment Protocol: A typical dTMS treatment protocol for OCD involves multiple sessions administered over several weeks. The specific parameters, such as the frequency, intensity, and duration of each session, will be determined by the healthcare provider based on the patient’s needs and response to treatment.

Safety and Side Effects: dTMS is generally considered safe with relatively mild side effects, such as mild discomfort or headache at the stimulation site. These side effects are typically temporary and well-tolerated. However, the treatment should be administered by trained professionals to ensure safety and effectiveness.

Efficacy: Research on the use of dTMS for OCD is still evolving, and the results have been mixed. Some studies have shown promising outcomes, with a reduction in OCD symptoms, while others have not demonstrated significant benefits. Response to dTMS can vary among individuals.

Individualized Treatment: The effectiveness of dTMS for OCD, like other treatment options, can vary from person to person. The suitability of dTMS as a treatment for a specific individual should be determined through a comprehensive evaluation by a qualified mental health professional.

McCathern et al. evaluate the current research on the effectiveness of dTMS therapy for individuals with treatment-resistant OCD. This review also investigates shortcomings in current dTMS research and the hypothesized future of dTMS therapy ¹⁾

Roth et al. analyzed data from a double-blind multicenter dTMS study and found the efficacy of this novel treatment even in OCD patient cohorts who previously failed to respond to multiple medications and CBT ²⁾.

Whether dTMS affects depression symptoms similarly to cognitive behavioral therapy (CBT) remains to be examined.

The study employed a random intercept cross-lagged panel model (RI-CLPM) to examine the relationship of OCD and depression symptoms in 94 treatment-refractory patients, undergoing dTMS or sham treatment.

Both OCD and depression symptoms improved significantly. However, a stable, cross-lagged relationship between the variables was not supported. Changes in one symptom domain could not be used to predict the other.

The present study was conducted in a treatment-refractory population, meaning the present findings may not generalize to treatment patients or those with less severe OCD symptoms. It is unclear whether the study was sufficiently powered to detect the effects of interest, and this concern also meant that examining the dTMS and sham groups independently was not feasible.

When treating OCD with dTMS, depression symptoms appear likely to diminish but should be monitored throughout, and additional interventions applied if needed ³⁾.

The study provides valuable insights into the potential benefits of dTMS for treatment-refractory patients with OCD and comorbid depression symptoms. However, it also highlights limitations related to generalizability and statistical power, emphasizing the need for further research to better understand the interplay between OCD and depression symptoms in various patient populations. Additionally, it underscores the importance of ongoing monitoring and a holistic approach to mental health treatment.

Ikawa et al. conducted an FDA-approved dTMS protocol for 26 patients with OCD. In addition, individual exposure stimulation that elicited each patient’s obsessive thoughts was also combined during dTMS treatment. Before and after 30 sessions of TMS treatment, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to assess changes in the severity of each patient’s obsessive-compulsive disorder. Response to dTMS treatment in patients with OCD was determined by whether the total score on the Y-BOCS after a course of treatment was reduced by 30% or more compared with the score at baseline. The percentage of responders in this case series following the 30 sessions of dTMS treatment was 53.9%. In addition, total Y-BOCS scores and scores on each item were significantly improved. The percent changes in total Y-BOCS scores did not differ between the sexes or between on- and off-medication patients. No obvious adverse events were observed in this case series. In line with the results of TMS studies for OCD patients reported overseas, dTMS treatment for Japanese patients with OCD may have a favorable therapeutic effect ⁴⁾

The study conducted by Ikawa et al. presents promising results for the use of dTMS in the treatment of OCD. The response rate, improvements in Y-BOCS scores, and the absence of adverse events are positive indicators. However, further research with larger sample sizes, control groups, and long-term follow-up is needed to confirm the efficacy of dTMS for OCD and to understand its place in the broader spectrum of OCD treatments.

Latest PubMed Deep Transcranial magnetic stimulation for obsessive-compulsive disorder treatment Related Articles

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McCathern AG, Mathai DS, Cho RY, Goodman WK, Storch EA. Deep transcranial magnetic stimulation for obsessive compulsive disorder. Expert Rev Neurother. 2020 Oct;20(10):1029-1036. doi: 10.1080/14737175.2020.1798232. Epub 2020 Aug 1. PMID: 32684005.

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Roth Y, Barnea-Ygael N, Carmi L, Storch EA, Tendler A, Zangen A. Deep transcranial magnetic stimulation for obsessive-compulsive disorder is efficacious even in patients who failed multiple medications and CBT. Psychiatry Res. 2020 Aug;290:113179. doi: 10.1016/j.psychres.2020.113179. Epub 2020 Jun 3. PMID: 32540588.

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Smárason O, Boedeker PJ, Guzick AG, Tendler A, Sheth SA, Goodman WK, Storch EA. Depressive symptoms during deep transcranial magnetic stimulation or sham treatment for obsessive-compulsive disorder. J Affect Disord. 2023 Oct 16:S0165-0327(23)01257-0. doi: 10.1016/j.jad.2023.10.075. Epub ahead of print. PMID: 37852581.

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Ikawa H, Osawa R, Sato A, Mizuno H, Noda Y. A Case Series of Deep Transcranial Magnetic Stimulation Treatment for Patients with Obsessive-Compulsive Disorder in the Tokyo Metropolitan Area. J Clin Med. 2022 Oct 18;11(20):6133. doi: 10.3390/jcm11206133. PMID: 36294453; PMCID: PMC9605577.

Magnetic resonance imaging for idiopathic intracranial hypertension diagnosis

July 29, 2023

Magnetic Resonance Imaging (MRI) plays an essential role in idiopathic intracranial hypertension diagnosis.

When evaluating a patient suspected of having IIH, MRI is commonly used for the following purposes:

Exclude Other Causes: An MRI of the brain is performed to rule out other conditions that may present with similar symptoms. These may include brain tumors, venous sinus thrombosis, or other intracranial abnormalities.

Assessment of the Brain and Ventricular System: MRI provides detailed images of the brain and can show any structural abnormalities, such as brain masses, cysts, or hydrocephalus (abnormal accumulation of cerebrospinal fluid). These findings can help identify or rule out potential causes of increased intracranial pressure.

Visualization of the Optic Nerves: MRI allows for visualization of the optic nerves and can detect any swelling or abnormalities, which can be crucial in diagnosing IIH. Enlargement of the subarachnoid space around the optic nerves (perioptic subarachnoid space distension) is a common finding in IIH.

Measurement of the Cerebral Venous Sinuses: MRI can assess the patency and flow within the cerebral venous sinuses, which are large blood vessels that drain blood from the brain. Abnormalities in these sinuses may contribute to IIH.

Assessment of Intracranial Pressure and Blood Flow: Specialized MRI techniques, such as MR venography and phase-contrast imaging, can be used to indirectly estimate intracranial pressure and evaluate cerebrospinal fluid (CSF) dynamics.

Follow-up and Monitoring: MRI may be used to monitor the progression of the condition and the effectiveness of treatment over time.

It’s important to note that while MRI is an essential diagnostic tool, the diagnosis of IIH typically involves a combination of clinical evaluation, neuroimaging, and other tests, such as lumbar puncture (to measure CSF pressure) and visual field testing (to assess any impact on vision).

MRI and magnetic resonance venography findings are important tools in the diagnosis of IIH. Empty sella turcica, optic nerve protrusion, distension of the optic nerve sheath, optic nerve tortuosity, posterior globe flattening, and transverse sinus stenosis have been found to be the most promising diagnostic markers for IIH, although the absence of these findings does not rule out the diagnosis ¹⁾.

Bsteh et al. included patients from the Vienna-Idiopathic-Intracranial-Hypertension (VIIH) database with Idiopathic intracranial hypertension according to Friedman criteria and cranial MRI performed at diagnosis. The presence of empty sella (ES), perioptic subarachnoid space distension (POSD) with or without optic nerve tortuosity (ONT), posterior globe flattening (PGF) and transverse sinus stenosis (TSS) was assessed and multivariable regression models regarding visual outcome (persistent visual impairment/visual worsening) and headache outcome (headache improvement/freedom of headache) were fitted.

They included 84 IIH patients (88.1% female, mean age 33.5 years, median body mass index 33.7). At baseline, visual impairment was present in 70.2% and headache in 84.5% (54.8% chronic). Persistent visual impairment occurred in 58.3%, visual worsening in 13.1%, headache improvement was achieved in 83.8%, and freedom of headache in 26.2%. At least one MRI feature was found in 78.6% and 60.0% had ≥3 features with POSD most frequent (64.3%) followed by TSS (60.0%), ONT (46.4%), ES (44.0%), and PGF (23.8%). In multivariable models, there was no association of any single MRI feature or their number with visual impairment, visual worsening, headache improvement, or freedom. Visual impairment at baseline predicted persistent visual impairment (odds ratio 6.3, p<0.001), but not visual worsening. Chronic headache at baseline was significantly associated with a lower likelihood of headache freedom (odds ratio 0.48, p=0.013), but not with headache improvement.

MRI features of IIH are neither prognostic of visual nor headache outcome ²⁾.

In a retrospective, observational study included demographic and clinical data from 10 patients with IIH and 10 controls. Brain MRI findings in IIH patients were recorded twice: once when patients had papilledema and again after resolution of papilledema. Neuroradiologists graded MRI findings in both groups based on an imaging grading scale.

Results: After the resolution of papilledema, all patients showed improvement in 2 or more of the MRI characteristics of IIH. This was especially the case for the height of the midsagittal pituitary gland and optic nerve sheath thickness (ONST), which were significantly different in all pairwise group comparisons. Sellar configuration, globe configuration, and horizontal orbital optic nerve tortuosity were different between the IIH pre-treatment group and controls, but not between controls and the IIH post-treatment group. We found no difference in optic nerve head hyperintensity or optic nerve thickness among the 3 groups.

demonstrated that several morphometric MRI characteristics in IIH are reversible to a certain extent after treatment. Enlarged subarachnoid spaces filled with cerebrospinal fluid seem to remain reduced, and the ONST and height of the pituitary gland are not fully normalized after treatment ³⁾

Neuroimaging, usually with computed tomography (CT/CAT) or magnetic resonance imaging (MRI), is used to exclude any mass lesions. In IIH these scans typically appear to be normal, although small or slit-like ventricles, dilatation and buckling of the optic nerve sheaths and “empty sella sign” (flattening of the pituitary gland due to increased pressure) and enlargement of Meckel’s caves may be seen.

https://pedclerk.bsd.uchicago.edu/sites/pedclerk.uchicago.edu/files/uploads/pseudotumor_0.jpg

The protocol consists of a brain MRI and head magnetic resonance venography (MRV), both performed without and with intravenous gadolinium contrast material to minimize potential pitfalls of noncontrast MRV techniques and obviate ionizing radiation from CT/CT venography. Although low-field-strength MRI scanners may be sufficient to exclude large intracranial pathology, higher field strength (1.5 or 3.0 T) superconducting units are generally preferred to appreciate the imaging findings associated with chronically elevated ICP ⁴⁾.

see Magnetic resonance venography for idiopathic intracranial hypertension.

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Barkatullah AF, Leishangthem L, Moss HE. MRI findings as markers of idiopathic intracranial hypertension. Curr Opin Neurol. 2021 Feb 1;34(1):75-83. doi: 10.1097/WCO.0000000000000885. PMID: 33230036; PMCID: PMC7856277.

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Bsteh G, Marik W, Krajnc N, Macher S, Mitsch C, Pruckner P, Novak K, Wöber C, Pemp B. MRI features of idiopathic intracranial hypertension are not prognostic of visual and headache outcome. J Headache Pain. 2023 Jul 28;24(1):97. doi: 10.1186/s10194-023-01641-x. PMID: 37507663.

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Batur Caglayan HZ, Ucar M, Hasanreisoglu M, Nazliel B, Tokgoz N. Magnetic Resonance Imaging of Idiopathic Intracranial Hypertension: Before and After Treatment. J Neuroophthalmol. 2019 Sep;39(3):324-329. doi: 10.1097/WNO.0000000000000792. PMID: 31430269.

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https://academic.oup.com/neurosurgery/article/80/3/341/2901909/Imaging-of-Intracranial-Pressure-Disorders

Mild traumatic brain injury

June 6, 2023June 4, 2023

Latest mild traumatic brain injury- related PubMed Articles

Mild TBI, often called “concussion,” is defined by a GCS of 14 to 15 and accounts for over 80% of TBI ¹⁾.

see Mild traumatic brain injury definition.

Mild traumatic brain injury epidemiology.

see Mild Traumatic Brain Injury Classification.

see Mild Traumatic Brain Injury Biomarkers.

S100B in mild traumatic brain injury

Recommendation: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3211100/

The initial ionic flux and glutamate release result in significant energy demands and a period of metabolic crisis for the injured brain. These physiological perturbations can now be linked to clinical characteristics of concussion, including migrainous symptoms, vulnerability to repeat injury, and cognitive impairment. Furthermore, advanced neuroimaging now allows a research window to monitor postconcussion pathophysiology in humans noninvasively. There is also increasing concern about the risk for chronic or even progressive neurobehavioral impairment after concussion/mild traumatic brain injury. Critical studies are underway to better link the acute pathobiology of concussion with potential mechanisms of chronic cell death, dysfunction, and neurodegeneration ²⁾.

Glutamate release and ionic disequilibrium

As a result of mechanical trauma, neuronal cell membranes and axons undergo disruptive stretching, leading to temporary ionic disequilibrium ³⁾.

As a result, levels of extracellular potassium increase drastically, and indiscriminate glutamate release occurs ⁴⁾.

Glutamate release activates N-methyl-D-aspartate receptors, which leads to accumulation of intracellular calcium ⁵⁾ ⁶⁾ ⁷⁾ , causing mitochondrial respiration dysfunction, protease activation, and often initiating apoptosis ⁸⁾ ⁹⁾. Elevated glutamate levels were also found to be significantly correlated with derangements in lactate, potassium, brain tissue pH, and brain tissue CO2 levels in human studies ¹⁰⁾. Additionally, sodium channel upregulation, fueled by ATPase proteins depending on glucose for energy, is observed following axonal stretch injuries ¹¹⁾.

Energy crisis and mitochondrial dysfunction

In combination, the cellular response to the above-mentioned ionic shifts and the downstream effects of the neurotransmitter release lead to an acute energy crisis. This occurs when, to restore ionic equilibrium, adenosine-triphosphate (ATP) -dependent sodium-potassium ion transporter pump activity increases, which augments local cerebral glucose demand ¹²⁾.

Further metabolic demand is incurred by ATP-dependent sodium channel upregulation. This occurs in the face of mitochondrial dysfunction, leading cells to primarily utilize glycolytic pathways instead of aerobic metabolism for energy, and causing extracellular lactate accumulation as a byproduct ¹³⁾. This acidosis, caused by hyperglycolysis, has been shown to worsen membrane permeability, ionic disequilibrium, and cerebral edema ¹⁴⁾.

Some evidence shows that the lactate produced by this process may eventually be utilized as a source of energy by the neurons once mitochondrial oxidative respiration normalizes; in fact, one study showed that in moderate to severe TBI the incidence of abnormally high levels of lactate uptake were seen in 28% of subjects ¹⁵⁾. The same study showed that patients exhibiting a higher rate of brain lactate uptake relative to arterial lactate levels tended to have more favorable outcomes compared to others with lower relative lactate uptake.

Alterations in cerebral blood flow

Some studies have shown that cerebral blood flow decreases immediately following the insult, and the amount of time it remains lowered seems to depend on the severity of the injury ¹⁶⁾ ¹⁷⁾.

Other studies, however, show no significant differences in CBF following mild TBI in subjects over 30 years of age ¹⁸⁾. In pediatric studies, CBF has been seen to increase during the first day following mild TBI, followed by decreased CBF for many days after ¹⁹⁾ ²⁰⁾. Data comparing cerebral blood flow in pediatric TBI patients has shown impaired autoregulation in 42% of moderate and severe and 17% of mild injuries ²¹⁾.

Histopathologic changes

The underlying histopathologic changes that occur are relatively unknown. In order to improve understanding of acute injury mechanisms, appropriately designed pre-clinical models must be utilized.

The clinical relevance of compression wave injury models revolves around the ability to produce consistent histopathologic deficits. Mild traumatic brain injuries activate similar neuroinflammatory cascades, cell death markers and increases in amyloid precursor protein in both humans and rodents. Humans, however, infrequently succumb to mild traumatic brain injuries and, therefore, the intensity and magnitude of impacts must be inferred. Understanding compression wave properties and mechanical loading could help link the histopathologic deficits seen in rodents to what might be happening in human brains following concussions ²²⁾.

see Mild traumatic brain injury clinical features.

see Mild traumatic brain injury diagnosis.

Mild traumatic brain injury guideline

Mild traumatic brain injury treatment.

see Mild traumatic brain injury complications.

Mild traumatic brain injury case series.

Mild traumatic brain injury case reports.

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Ginsburg J, Huff JS. Closed Head Trauma. 2023 Feb 7. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32491784.

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Giza CC, Hovda DA. The new neurometabolic cascade of concussion. Neurosurgery. 2014 Oct;75 Suppl 4:S24-33. doi: 10.1227/NEU.0000000000000505. PubMed PMID: 25232881.

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Farkas O, Lifshitz J, Povlishock JT. Mechanoporation induced by diffuse traumatic brain injury: an irreversible or reversible response to injury? J Neurosci. 2006 Mar 22;26(12):3130–3140.

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Katayama Y, Becker DP, Tamura T, Hovda DA. Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg. 1990 Dec;73(6):889–900.

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Osteen CL, Giza CC, Hovda DA. Injury-induced alterations in N-methyl-D-aspartate receptor subunit composition contribute to prolonged 45 calcium accumulation following lateral fluid percussion. Neuroscience. 2004;128(2):305–322.

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Osteen CL, Moore AH, Prins ML, Hovda DA. Age-dependency of 45calcium accumulation following lateral fluid percussion: acute and delayed patterns. J Neurotrauma. 2001 Feb;18(2):141–162.

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Fineman I, Hovda DA, Smith M, Yoshino A, Becker DP. Concussive brain injury is associated with a prolonged accumulation of calcium: a 45Ca autoradiographic study. Brain Research. 1993;624(1–2):94–102.

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Raghupathi R. Cell death mechanisms following traumatic brain injury. Brain Pathol. 2004 Apr;14(2):215–222.

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Sullivan PG, Rabchevsky AG, Waldmeier PC, Springer JE. Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death? J Neurosci Res. 2005 Jan 1–15;79(1–2):231–239.

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Reinert M, Hoelper B, Doppenberg E, Zauner A, Bullock R. Substrate delivery and ionic balance disturbance after severe human head injury. Acta Neurochir Suppl. 2000;76:439–444.

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Yuen TJ, Browne KD, Iwata A, Smith DH. Sodium channelopathy induced by mild axonal trauma worsens outcome after a repeat injury. J Neurosci Res. 2009 Dec;87(16):3620–3625.

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Yoshino A, Hovda DA, Kawamata T, Katayama Y, Becker DP. Dynamic changes in local cerebral glucose utilization following cerebral concussion in rats: evidence of a hyper- and subsequent hypometabolic state. Brain Research. 1991;561(1):106–119.

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Kawamata T, Katayama Y, Hovda DA, Yoshino A, Becker DP. Lactate accumulation following concussive brain injury: the role of ionic fluxes induced by excitatory amino acids. Brain Research. 1995;674(2):196–204.

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Kalimo H, Rehncrona S, Soderfeldt B. The role of lactic acidosis in the ischemic nerve cell injury. Acta Neuropathol Suppl (Berl) 1981;7:20–22.

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Glenn TC, Kelly DF, Boscardin WJ, et al. Energy dysfunction as a predictor of outcome after moderate or severe head injury: indices of oxygen, glucose, and lactate metabolism. J Cereb Blood Flow Metab. 2003 Oct;23(10):1239–1250.

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Golding EM, Steenberg ML, Contant CF, Jr, Krishnappa I, Robertson CS, Bryan RM., Jr Cerebrovascular reactivity to CO(2) and hypotension after mild cortical impact injury. Am J Physiol. 1999 Oct;277(4 Pt 2):H1457–1466.

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Grindel SH. Epidemiology and pathophysiology of minor traumatic brain injury. Curr Sports Med Rep. 2003 Feb;2(1):18–23.

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Chan KH, Miller JD, Dearden NM. Intracranial blood flow velocity after head injury: relationship to severity of injury, time, neurological status and outcome. J Neurol Neurosurg Psychiatry. 1992 Sep;55(9):787–791.

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Mandera M, Larysz D, Wojtacha M. Changes in cerebral hemodynamics assessed by transcranial Doppler ultrasonography in children after head injury. Childs Nerv Syst. 2002 Apr;18(3–4):124–128.

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Becelewski J, Pierzchala K. Cerebrovascular reactivity in patients with mild head injury. Neurol Neurochir Pol. 2003 Mar-Apr;37(2):339–350.

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Vavilala MS, Lee LA, Boddu K, et al. Cerebral autoregulation in pediatric traumatic brain injury. Pediatr Crit Care Med. 2004;5(3):257–263.

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Lucke-Wold BP, Phillips M, Turner RC, Logsdon AF, Smith KE, Huber JD, Rosen CL, Regele JD. Elucidating the role of compression waves and impact duration for generating mild traumatic brain injury in rats. Brain Inj. 2016 Nov 23:1-8. [Epub ahead of print] PubMed PMID: 27880054.

Trigeminal neuralgia

March 28, 2023

Latest Pubmed Related Articles

The facial pain syndrome known as trigeminal neuralgia was described more than 300 years ago ¹⁾.

Trigeminal neuralgia definition.

see Trigeminal neuralgia epidemiology.

see Trigeminal neuralgia classification.

see Trigeminal neuralgia pathogenesis.

see Trigeminal neuralgia pathophysiology.

Natural History

Typical trigeminal neuralgia caused by microvascular compression of the trigeminal nerve root in the posterior fossa may become transformed over time into atypical trigeminal neuralgia, if left untreated. This transformation involves change in the character of pain and development of sensory impairment. Two representative cases are presented to support this theory.

If the theory of progressive change in character of pain and degree of sensory impairment in the course of otherwise typical trigeminal neuralgia is correct, trigeminal neuralgia, atypical neuralgia, and trigeminal neuropathic pain may represent different degrees of injury to the trigeminal nerve, therefore comprising a continuous spectrum rather than discrete diagnoses ²⁾.

Trigeminal neuralgia clinical features.

Barrow Neurological Institute Pain Scale.

Barrow Neurological Facial Numbness Scale.

Slavin KV. Commentary: Development and Evaluation of a Preoperative Trigeminal Neuralgia Scoring System to Predict Long-Term Outcome Following Microvascular Decompression. Neurosurgery. 2019 Dec 9. pii: nyz540. doi: 10.1093/neuros/nyz540. [Epub ahead of print] PubMed PMID: 31813971.

Trigeminal neuralgia diagnosis.

see Trigeminal neuralgia treatment.

see Trigeminal neuralgia outcome.

see Trigeminal neuralgia case series.

see Trigeminal neuralgia case reports.

¹⁾

Lewy FH: The first authentic case of major trigeminal neuralgia and some comments on the history of this disease. Ann Med Hist 10:247–250, 1938.

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Burchiel KJ, Slavin KV. On the natural history of trigeminal neuralgia. Neurosurgery. 2000 Jan;46(1):152-4; discussion 154-5. Review. PubMed PMID: 10626945.

Condoliase for lumbar disc herniation

February 23, 2023

Latest Pubmed Related Articles

Percutaneous chemonucleolysis with condoliase has been available for painful lumbar disc herniation since 2018 in Japan.

In the 1980s, chemonucleolysis with chymopapain, a protease, was widely used as the intermediate treatment between conservative therapy and surgical therapy in Western countries. However, since chymopapain was withdrawn from the market in 2002 for non-scientific commercial reasons, chemonucleolysis has not been a therapeutic option for LDH. Condoliase (chondroitin sulfate ABC endolyase), a glycosaminoglycan-degrading enzyme, was approved by the drug regulatory authority in Japan as a newer intradiscal therapy for LDH after clinical studies conducted in Japan demonstrated efficacy and safety for patients with LDH ¹⁾

Condoliase as a first-line treatment option ahead of surgical treatment for LDH is superior, from a cost perspective to surgical treatment from the beginning. Condoliase is also a cost-effective alternative to non-surgery conservative treatment ²⁾.

Patients between 20 and 70 years of age with unilateral leg pain, positive findings on the straight leg raise test, and LDH were recruited. All eligible patients were randomly assigned to receive condoliase (1.25, 2.5, or 5 U) or placebo. The primary end point was a change in the worst leg pain from preadministration (baseline) to week 13. The secondary end points were changes from baseline in the following items: worst back pain, Oswestry Disability Index (ODI), SF-36, and neurological examination. For pharmacokinetic and pharmacodynamic analyses, plasma condoliase concentrations and serum keratan sulfate concentrations were measured. The safety end points were adverse events (AEs) and radiographic and MRI parameters. Data on leg pain, back pain, abnormal neurological findings, and imaging parameters were collected until week 52. RESULTS A total of 194 patients received an injection of condoliase or placebo. The mean change in worst leg pain from baseline to week 13 was -31.7 mm (placebo), -46.7 mm (1.25 U), -41.1 mm (2.5 U), and -47.6 mm (5 U). The differences were significant at week 13 in the 1.25-U group (-14.9 mm; 95% CI -28.4 to -1.4 mm; p = 0.03) and 5-U group (-15.9 mm; 95% CI -29.0 to -2.7 mm; p = 0.01) compared with the placebo group. The dose-response improvement in the worst leg pain at week 13 was not significant (p = 0.14). The decrease in the worst leg pain in all 3 condoliase groups was observed from week 1 through week 52. Regarding the other end points, the worst back pain and results of the straight leg raise test, ODI, and SF-36 showed a tendency for sustained improvement in each of the condoliase groups until week 52. In all patients at all time points, plasma condoliase concentrations were below the detectable limit (< 100 μU/ml). Serum keratan sulfate concentrations significantly increased from baseline to 6 hours and 6 weeks after administration in all 3 condoliase groups. No patient died or developed anaphylaxis or neurological sequelae. Five serious AEs occurred in 5 patients (3 patients in the condoliase groups and 2 patients in the placebo group), resolved, and were considered unrelated to the investigational drug. Severe AEs occurred in 10 patients in the condoliase groups and resolved or improved. In the condoliase groups, back pain was the most frequent AE. Modic type 1 change and decrease in disc height were frequent imaging findings. Dose-response relationships were observed for the incidence of adverse drug reactions and decrease in disc height. CONCLUSIONS Condoliase significantly improved clinical symptoms in patients with LDH and was well tolerated. While all 3 doses had similar efficacy, the incidence of adverse drug reactions and decrease in disc height were dose dependent, thereby suggesting that 1.25 U would be the recommended clinical dose of condoliase. Clinical trial registration no.: NCT00634946 (clinicaltrials.gov) ³⁾.

Ohtonari et al. investigated clinical and radiographic outcomes three months after the administration because secondary surgical removal is most required during this period for insufficient pain relief, and analyzed whether the differences in intradiscal injection areas affected the clinical outcomes. They retrospectively investigated 47 consecutive patients (males, 31; median age, 40 years) three months after the administration. Clinical outcomes were evaluated using the Japanese Orthopaedic Association Back Pain Questionnaire (JOABPEQ), a visual analog scale (VAS) score for low back pain, and VAS scores for pains and numbness in the lower limbs. Radiographic outcomes were analyzed in 41 patients, using parameters such as mid-sagittal disc height and maximal protrusion length of herniation on MRI preoperatively and at the final follow-up. The postoperative median evaluation period was 90 days. The effective rate of low back pain based on the pain-related disorders at baseline and the last follow-up in the JOABPEQ reached 79.5%. The postoperative proportion of VAS scores recovery ≥ 2 points and ≥ 50% for pains in the lower limbs were 80.9% and 66.0%, respectively, revealing satisfactory effectiveness. Preoperative median mid-sagittal disc height significantly reduced from 9.5 to 7.6 mm postoperatively. There were no significant differences in pain relief in the lower limbs by injection areas in the center and the dorsal 1/3rd near the herniation of the nucleus pulposus. Chemonucleolysis with condoliase revealed satisfactory short-term outcomes after the administration regardless of intradiscal injection areas ⁴⁾.

101 patients who underwent chemonucleolysis with condoliase from January 2019 to December 2021. Patients were divided into good outcome (i.e., favorable outcome) and poor outcome (i.e., requiring additional surgical treatment) groups. Patient demographics and imaging findings were collected. Clinical outcomes were evaluated using the numerical rating scale and Japanese Orthopaedic Association scores at baseline and at 1- and 3-month follow-up. Pretreatment indicators for additional surgery were compared between the 2 groups. Results: There was a significant difference in baseline leg numbness between the good outcome and poor outcome groups (6.27 ± 1.90 vs. 4.42 ± 2.90, respectively; p = 0.033). Of the 101 included patients, 32 received a preoperative computed tomography scan. In those patients, the presence of calcification or ossification in disc hernia occurred more often in the poor outcome group (61.5% vs. 5.3%, respectively; p < 0.001; odds ratio = 22.242; p = 0.014). Receiver-operating characteristics curve analysis for accompanying calcification or ossification showed an area under the curve of 0.858 (95% confidence interval, 0.715-1.000; p = 0.001). Conclusions: Calcified or ossified disc herniation may be useful predictors of unsuccessful treatment in patients with condoliase administration ⁵⁾.

Sixty-seven patients (44 men, 23 women; mean age, 46.7 ± 18.0 years) were analyzed. Time-course changes in disc height, disc degeneration, and herniation size were assessed. For clinical outcomes assessment, visual analog scale (VAS) scores for leg and back pain and the Oswestry disability index (ODI) were obtained at baseline and the 3-month, 1-year, and 2-year follow-ups. We obtained a questionnaire from these patients at two years to assess satisfaction and recommendation. Condoliase therapy was considered to be effective in patients whose VAS score for leg pain improved by ≥ 50% at 2 years from baseline and who did not require surgery.

Results: Condoliase therapy was effective in 51 patients (76.1%). Eight patients (11.9%) required surgery due to ineffectiveness of the therapy. Condoliase therapy was ineffective in five out of six patients with a history of discectomy. The ODI and VAS scores for leg and back pain significantly improved from three months to two years. Of the patients, 80% satisfied with their outcomes, and 85% recommended this therapy. Progression of disc degeneration was observed in 57.1% of patients at three months; however, 30% recovered to baseline at two years. The mean disc height decreased at three months, but recovered slightly at one year and remained stable until two years. No recurrent disc herniation was observed.

Conclusions: Chemonucleolysis with condoliase was effective in 78% of patients with LDH for 2 years. Chemonucleolysis-induced disc degeneration was slightly recovered and maintained for two years post-injection. This treatment resulted in high patient satisfaction and recommendations ⁶⁾.

137 LDH patients treated through condoliase at four Japanese institutions and assessed its effectiveness among different age categories on alleviation of visual analog scale (VAS) of leg pain, low back pain and numbness, as well as ODI and JOA scores. Moreover, we divided them into either a “group-A” category if a ≥50% improvement in baseline leg pain VAS was observed or “group-N” if VAS leg pain improved <50%. Next, we assessed the differences in clinical and demographic distribution between group-A and group-N. Results: Fifty-five patients were classified as group-A (77.5%) and 16 patients were allocated to group-N (22.5%). A significant difference in Pfirrmann classification was found between both cohorts, with grade IV suggested to be most receptive. A posterior disc angle > 5° was also found to approach statical significance. In all age groups, average VAS scores showed improvement. However, 75% of adolescent patients showed deterioration in Pfirrmann classification following treatment. Conclusions: Intradiscal condoliase injection is an effective treatment for LDH, even in patients with large vertebral translation and posterior disc angles, regardless of age. However, since condoliase imposes a risk of progressing disc degeneration, its indication for younger patients remains controversial ⁷⁾.

Medical records and radiographic findings were reviewed retrospectively for 127 patients with LDH (88 male, 39 female, mean age: 46.6 ± 17.1 years, mean follow-up: 9.8 ± 7.8 months) who underwent chemonucleolysis with intradiscal condoliase injection at our center since September 2018. Condoliase (1.25 U/mL; 1 mL volume) was injected toward the middle of the affected intervertebral nucleus pulposus using a 21-gauge disc-puncture needle.

Results: Cases in which the Pfirrmann grade did and did not progress in the 3 months after the injection were included in groups P (progression, n = 49) and NP (non-progression, n = 78), respectively. Logistic regression analysis of progression of Pfirrmann grade post-injection showed significant associations with age <40 years (p = 0.013, odds ratio (OR): 3.69, 95% confidence interval (CI): 1.32-10.31), Pfirrmann Grade II or III at baseline (p = 0.021, OR: 3.51, 95% CI: 1.24-9.64), and a high-intensity MRI signal in the herniation (p = 0.047, OR: 2.97, 95% CI: 1.03-8.87). Patients in group P had significantly higher rates of disc height decrease ≥20%, reduced herniated disc size, and improved VAS for pain, but both groups had significant decreases in pain. No cases had an anaphylactic shock or neurologic sequelae.

Conclusions: These results show the safety and efficacy of chemonucleolysis with condoliase for treatment of painful LDH. Progression of Pfirrmann criteria on MRI at 3 months after injection was significantly associated with an improved clinical outcome ⁸⁾.

Seventy patients (85.4%) were classified into the effective (E) group and 12 patients (14.6%) into the less-effective (L) group. Surgical treatment was required in four patients. No severe adverse complications were reported; 41.3% of the patients developed disc degeneration of Pfirrmann grade 1 or more at the injected disc level. Univariate analysis revealed that young age (p = 0.036), without history of epidural or nerve root block (p = 0.024), and injection into the central portion of the intervertebral disc (p = 0.014) were significantly associated with clinical effectiveness. A logistic regression analysis revealed that injection into the central portion of the intervertebral disc (p = 0.049; odds ratio, 4.913; 95% confidence interval, 1.006-26.204) was significantly associated with clinical effectiveness.

Conclusions: Chemonucleolysis with condoliase is a safe and effective treatment for painful LDH; 85.4% of the patients showed improvement after the treatment without severe adverse events. To obtain the best outcome, condoliase should be injected into the center of the intervertebral disc ⁹⁾.

Forty-seven patients (20 women, 27 men; mean age 48 years) were included. The herniation level was L2/3 in one patient, L3/4 in two, L4/5 in 23, and L5/S1 in 21. Median symptom duration was 8 months. The mean VAS and ODI improved significantly from the baseline to 3-month follow-up (p < 0.01). Group E included 33 patients (70.2%) and group I included 14, three of whom had a history of discectomy. The rates of spondylolisthesis and posterior intervertebral angle ≥5° were significantly higher in group I than in group E. However, the rates of trans-ligamentous type and herniation with high signal intensity on T2-weighted images (highT2) were significantly higher in group E. Reduction of disc herniation was more frequently observed in group E.

Conclusions: Condoliase injection resulted in significantly improved symptoms in patients with LDH. Condoliase therapy was less effective for patients with a history of discectomy, spondylolisthesis, or those with a posterior intervertebral angle ≥5°, while trans-ligamentous type and high T2 herniation were associated with increased efficacy ¹⁰⁾

A total of 52 patients (mean age, 45.0 years) were enrolled and classified according to whether the injection was effective (E group, n=40, 76.9%) or less effective (L group, n=9, 17.3%). Three patients (5.8%) underwent herniotomy for residual pain within 6 months of the injection. There were no severe adverse events. Reduction of herniation was seen on MRI more often in the E group than in the L group. The effectiveness in patients with transligamentous LDH was similar to that in patients with subligamentous LDH. High-intensity signal change in the area of LDH on pretreatment T2-weighted MRI was a significant predictor of successful leg pain relief.

Conclusions: An intradiscal condoliase injection was a safe and effective treatment for painful radiculopathy caused by LDH. Leg pain was more likely to improve in patients with high-intensity signal change in the area of LDH before treatment ¹¹⁾.

In total, 84 patients were recruited (52 men, 32 women; mean age, 44.2 ± 17.1 [16-86 years]). The duration of illness was 6.7 ± 6.8 (1.5-30) months. All patient-based outcomes significantly improved at 4 weeks after the administration compared with pretreatment. The intervertebral disc height decreased significantly at four weeks after condoliase administration compared with that before administration. Progression of intervertebral disc degeneration occurred in 50% of the patients. Eleven patients underwent herniotomy due to poor treatment effects. Moreover, treatment in 77.4% of the patients was considered effective. A logistic regression analysis revealed that L5/S1 disk administration (p = 0.029; odds ratio, 5.94; 95% confidence interval, 1.20-29.45) were significantly associated with clinical effectiveness.

Conclusions: Condoliase disk administration improved pain and quality of life over time. Condoliase disk administration was more effective in L5/S1 intervertebral administration ¹²⁾.

47 patients who received condoliase, 34 were enrolled in this study. The mean age of the patients was 33 years. The average duration since the onset of disease was 8.6 months. We evaluated patients’ low back and leg pain using a numerical rating scale (NRS) score at two time points (before therapy and 3 months after therapy). We divided the patients into two groups (good group (G): NRS score improvement ≥ 50%, poor group (P): NRS score improvement < 50%). The parameters evaluated were age, disease duration, body mass index (BMI), and positive or negative straight leg raising test results. In addition, the loss of disc height and preoperative radiological findings were evaluated. Results: In terms of low back and leg pain, the G group included 9/34 (26.5%) and 21/34 (61.8%) patients, respectively. Patients’ age (low back pain G/P, 21/36.5 years) was significantly lower in the G group for low back pain (p = 0.001). High-intensity change in the protruded nucleus pulposus (NP) and spinal canal occupancy by the NP ≥ 40% were significantly high in those with leg pain in the G groups (14/21, p = 0.04; and 13/21, p = 0.03, respectively). Conclusions: The efficacy of improvement in leg pain was significantly correlated with high-intensity change and size of the protruded NP. Condoliase was not significantly effective for low back pain but could have an effect on younger patients ¹³⁾.

42 patients with LDH who underwent intradiscal condoliase injection. Patients with and without a ≥50% improvement from baseline of leg pain at 3 months after injection were defined as responders and non-responders, respectively. Clinical features and radiological findings were compared between these groups.

Results: Of the 42 patients, 32 (76.2%) were responders and 10 (23.8%) were non-responders. Of 8 patients with a history of discectomy at the same level as LDH, 6 (75.0%) were responders. Non-responders had a significantly longer time from onset to treatment, smaller herniated volume before treatment, lower percentage reduction of herniated mass, and less intervertebral disc degeneration before treatment. There were no significant differences in LDH types (subligamentous extrusion or transligamentous extrusion types), high-intensity area within the herniation, changes in disc height, and region of condoliase injection between the two groups.

Conclusions: Intradiscal condoliase injection had a good short-term therapeutic effect in patients with LDH, including in transligamentous extrusion-type and revision cases as well as subligamentous extrusion-type cases. Administration of intradiscal condoliase injection may be most effective in patients with a larger herniated mass volume before treatment, and least effective in cases with a longer time and less intervertebral disc degeneration before treatment ¹⁴⁾.

A total of 82 and 81 patients received an injection of condoliase and placebo, respectively. The average changes in worst leg pain from baseline to week 13 (primary endpoint) were -49.5 mm in the condoliase group and -34.3 mm in the placebo group, and the difference of -15.2 mm was significant (95% confidence interval, -24.2 to -6.2; P = 0.001). Significant improvements were observed in the condoliase groups, compared with the placebo group, in most secondary endpoints at 1 year after administration. In the condoliase group, back pain, Modic type 1 change, and decrease in disc height were frequently reported, without any clinically relevant consequences.

Conclusion: Condoliase significantly improved symptoms in patients with LDH and was well tolerated. Condoliase is a novel and potent chemonucleolytic drug for the treatment of LDH ¹⁵⁾.

It has been available for painful lumbar disc herniation since 2018 in Japan.

A 25-year-old man with a history of LDH in L4/5, who underwent transforaminal full endoscopic lumbar discectomy when he was 17 years old, complained of severe pain radiating to his left leg for 1 month. The straight leg-raising test was limited to 25° on the left side. Lumbar T2-weighted magnetic resonance imaging (MRI) showed intracanal, left-sided transligamentous disc herniation at L4/5 with high-signal intensity. Because the conservative treatment with oral analgesics and selective left L5 nerve root block failed, the patient requested intradiscal condoliase injection instead of revision surgery. There were no adverse events reported after the condoliase treatment, and the pain radiating to the left leg improved within 2 weeks. A lumbar MRI performed 2 months after treatment revealed that the disc herniation had significantly decreased in size. The straight leg-raising test examined 3 months after treatment was negative. In this case, the disc herniation was of the transligamentous type and showed a high-signal intensity on T2-weighted MRI which could be suitably treated by condoliase injection therapy. This case report is the first to suggest that intradiscal condoliase injection could be a useful and novel conservative treatment option to treat postoperative rec-LDH ¹⁶⁾.

¹⁾

Matsuyama Y, Chiba K. Condoliase for treatment of lumbar disc herniation. Drugs Today (Barc). 2019 Jan;55(1):17-23. doi: 10.1358/dot.2019.55.1.2899445. PMID: 30740609.

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Takaki S, Miyama H, Iwasaki M. Cost-effectiveness analysis of intradiscal condoliase injection vs. surgical or conservative treatment for lumbar disc herniation. J Med Econ. 2023 Jan-Dec;26(1):233-242. doi: 10.1080/13696998.2023.2173465. PMID: 36794375.

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Matsuyama Y, Chiba K, Iwata H, Seo T, Toyama Y. A multicenter, randomized, double-blind, dose-finding study of condoliase in patients with lumbar disc herniation. J Neurosurg Spine. 2018 May;28(5):499-511. doi: 10.3171/2017.7.SPINE161327. Epub 2018 Feb 9. PMID: 29424676.

⁴⁾

Ohtonari T, Torii R, Noguchi S, Kitagawa T, Nishihara N. Short-term clinical and radiographic outcomes of chemonucleolysis with condoliase for painful lumbar disc herniation and analysis regarding intradiscal injection area. Neurosurg Rev. 2023 Feb 23;46(1):59. doi: 10.1007/s10143-023-01966-w. PMID: 36813932.

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Takeuchi S, Hanakita J, Takahashi T, Inoue T, Minami M, Suda I, Nakamura S, Kanematsu R. Predictive Factors for Poor Outcome following Chemonucleolysis with Condoliase in Lumbar Disc Herniation. Medicina (Kaunas). 2022 Dec 18;58(12):1868. doi: 10.3390/medicina58121868. PMID: 36557070; PMCID: PMC9781337.

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Banno T, Hasegawa T, Yamato Y, Yoshida G, Arima H, Oe S, Ide K, Yamada T, Kurosu K, Nakai K, Matsuyama Y. Condoliase therapy for lumbar disc herniation -2 year clinical outcome. J Orthop Sci. 2022 Nov 21:S0949-2658(22)00317-7. doi: 10.1016/j.jos.2022.11.005. Epub ahead of print. PMID: 36424250.

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Oshita Y, Matsuyama D, Sakai D, Schol J, Shirasawa E, Emori H, Segami K, Takahashi S, Yagura K, Miyagi M, Saito W, Imura T, Nakazawa T, Inoue G, Hiyama A, Katoh H, Akazawa T, Kanzaki K, Sato M, Takaso M, Watanabe M. Multicenter Retrospective Analysis of Intradiscal Condoliase Injection Therapy for Lumbar Disc Herniation. Medicina (Kaunas). 2022 Sep 15;58(9):1284. doi: 10.3390/medicina58091284. PMID: 36143959; PMCID: PMC9501482.

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Kobayashi K, Sato K, Ando T. Factors associated with disc degeneration based on Pfirrmann criteria after condoliase treatment for lumbar disc herniation. J Orthop Sci. 2022 Aug 24:S0949-2658(22)00230-5. doi: 10.1016/j.jos.2022.08.001. Epub ahead of print. PMID: 36030156.

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Okada E, Suzuki S, Nori S, Tsuji O, Nagoshi N, Yagi M, Fujita N, Nakamura M, Matsumoto M, Watanabe K. The effectiveness of chemonucleolysis with condoliase for treatment of painful lumbar disc herniation. J Orthop Sci. 2021 Jul;26(4):548-554. doi: 10.1016/j.jos.2020.06.004. Epub 2020 Jul 23. PMID: 32713796.

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Banno T, Hasegawa T, Yamato Y, Yoshida G, Yasuda T, Arima H, Oe S, Ushirozako H, Yamada T, Ide K, Watanabe Y, Matsuyama Y. Clinical outcome of condoliase injection treatment for lumbar disc herniation: Indications for condoliase therapy. J Orthop Sci. 2021 Jan;26(1):79-85. doi: 10.1016/j.jos.2020.02.002. Epub 2020 Feb 25. PMID: 32111547.

¹¹⁾

Hirai T, Takahashi T, Tanaka T, Motoyoshi T, Matsukura Y, Yuasa M, Inose H, Yoshii T, Okawa A. Intradiscal Injection with Condoliase (Chondroitin Sulfate ABC Endolyase) for Painful Radiculopathy Caused by Lumbar Disc Herniation. Spine Surg Relat Res. 2021 Oct 11;6(3):252-260. doi: 10.22603/ssrr.2021-0151. PMID: 35800623; PMCID: PMC9200423.

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Inoue M, Sainoh T, Kojima A, Yamagata M, Morinaga T, Mannoji C, Ataka H, Yamashita M, Takahashi H, Saito J, Fujiyoshi T, Ishikawa T, Eguchi Y, Kato K, Orita S, Inage K, Shiga Y, Norimoto M, Umimura T, Shiko Y, Kawasaki Y, Aoki Y, Ohtori S. Efficacy and Safety of Condoliase Disc Administration as a New Treatment for Lumbar Disc Herniation. Spine Surg Relat Res. 2021 Jun 11;6(1):31-37. doi: 10.22603/ssrr.2021-0035. PMID: 35224244; PMCID: PMC8842352.

¹³⁾

Ishibashi K, Fujita M, Takano Y, Iwai H, Inanami H, Koga H. Chemonucleolysis with Chondroitin Sulfate ABC Endolyase for Treating Lumbar Disc Herniation: Exploration of Prognostic Factors for Good or Poor Clinical Outcomes. Medicina (Kaunas). 2020 Nov 19;56(11):627. doi: 10.3390/medicina56110627. PMID: 33228119; PMCID: PMC7699387.

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Nakajima H, Kubota A, Maezawa Y, Watanabe S, Honjoh K, Ohmori H, Matsumine A. Short-Term Outcome and Predictors of Therapeutic Effects of Intradiscal Condoliase Injection for Patients with Lumbar Disc Herniation. Spine Surg Relat Res. 2020 Nov 20;5(4):264-271. doi: 10.22603/ssrr.2020-0126. PMID: 34435150; PMCID: PMC8356240.

¹⁵⁾

Chiba K, Matsuyama Y, Seo T, Toyama Y. Condoliase for the Treatment of Lumbar Disc Herniation: A Randomized Controlled Trial. Spine (Phila Pa 1976). 2018 Aug 1;43(15):E869-E876. doi: 10.1097/BRS.0000000000002528. PMID: 29257028.

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Funayama T, Setojima Y, Shibao Y, Noguchi H, Miura K, Eto F, Sato K, Kono M, Asada T, Takahashi H, Tatsumura M, Koda M, Yamazaki M. A Case of Postoperative Recurrent Lumbar Disc Herniation Conservatively Treated with Novel Intradiscal Condoliase Injection. Case Rep Orthop. 2022 Feb 15;2022:3656753. doi: 10.1155/2022/3656753. PMID: 35211348; PMCID: PMC8863464.

Tranexamic acid for intracranial meningioma

January 12, 2023

Latest Pubmed Articles

Intracranial meningioma surgery is often complicated by significant blood loss requiring blood transfusion with its attendant risks. Although tranexamic acid is used to reduce perioperative blood loss, its blood conservation effect is uncertain in neurosurgery.

Based upon Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Wijaya et al. from the Universitas Pelita Harapan, Tangerang, Banten, Indonesia, Cedars-Sinai Medical Center, Los Angeles, CES University, El Poblado, Medellín, Antioquia, Colombia. collected fully published English literature on the administration of tranexamic acid for patients undergoing intracranial meningioma surgery using the keywords [“tranexamic acid” and “meningioma”] and its synonyms from Cochrane Central Register of Controlled Trials Database, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and PubMed. The primary outcome of the current study was total blood loss. The secondary outcomes include individuals requiring blood transfusion, anesthesia duration, surgical duration, and complication rate. Each included study’s quality was assessed using the JADAD scale.

For qualitative and quantitative data synthesis, they included five RCTs (n = 321) with a mean age was 47.5 ± 11.9 years for the intervention group and 47.2 ± 11.9 years for the control group. The meta-analysis showed that the administration of TXA is associated with decreased total blood loss of standardized mean difference (SMD) of -1.40 (95% CI [-2.49, -0.31]), anesthetic time SMD -0.36 (95% CI [-0.63, -0.09]), and blood transfusion requirements RR 0.58 (95% CI [0.34, 0.99]).

The current study showed that TXA was associated with reduced intraoperative blood loss and intraoperative and postoperative blood transfusion. However, the studies are small. More RCT studies with a greater sample size are favorable ¹⁾.

Patients with supratentorial meningiomas and deemed suitable for surgical resection will be recruited in the trial. Patients will be randomized to receive either a single administration of 20 mg/kg TXA or a placebo of the same volume with a 1:1 allocation ratio after anesthesia induction. The primary endpoint is the cumulative incidence of early postoperative seizures within 7 days after craniotomy. Secondary outcomes include the incidence of non-seizure complications, changes in hemoglobin level from baseline, intraoperative blood loss, erythrocyte transfusion volume, Karnofsky Performance Status, all-cause mortality, length of stay, and total hospitalization cost.

Ethics and dissemination: This trial is registered at ClinicalTrial.gov and approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200224). The findings will be disseminated in peer-reviewed journals and presented at national or international conferences relevant to the subject fields.

Trial registration number: NCT04595786 ²⁾.

conducted a prospective, randomized double-blind clinical study. The patient scheduled to undergo excision of intracranial meningioma were randomly assigned to receive intraoperatively either intravenous TXA or placebo. Patients in the TXA group received an intravenous bolus of 20 mg/kg over 20 min followed by an infusion of 1 mg/kg/h up to surgical wound closure. Efficacy was evaluated based on total blood loss and transfusion requirements. Postoperatively, thrombotic complications, convulsive seizure, and hematoma formation were noted.

Ninety-one patients were enrolled and randomized: 45 received TXA (TXA group) and 46 received placebo (group placebo). Total blood loss was significantly decreased in the TXA group compared to the placebo (283 ml vs. 576 ml; P < 0.001). Transfusion requirements were comparable in the two groups (P = 0.95). The incidence of thrombotic complications, convulsive seizure, and hematoma formation were similar in the two groups.

TXA significantly reduces intraoperative blood loss but did not significantly reduce transfusion requirements in adults undergoing resection of intracranial meningioma ³⁾.

Thirty patients aged 18-65 years undergoing elective meningioma resection surgery were given either tranexamic acid or placebo (0.9% saline), tranexamic acid at a loading dose of 20 mg/kg, and infusion of 1 mg/kg/h during surgery. The intraoperative blood loss, coagulation profile, and the surgical field using the Likert scale were assessed.

The patients in the tranexamic group had significantly decreased intraoperative blood loss compared to the placebo group (616.42 ± 393.42 ml vs. 1150.02 ± 416.1 ml) (P = 0.02). The quality of the surgical field was better in the tranexamic group (median score 4 vs. 2 on Likert Scale) (P < 0.001). Patients in the tranexamic group had an improved coagulation profile and decreased blood transfusion requirement (p=0.016). The blood collected in the closed suction drain in 24 h postsurgery was less in the tranexamic acid group compared to the placebo group (84.7 ± 50.4 ml vs. 127.6 ± 62.2 ml) (P = 0.047).

Tranexamic acid bolus followed by infusion reduces perioperative blood loss by 46.43% and blood transfusion requirement with improved surgical field and coagulation profile in patients undergoing intracranial meningioma resection surgery ⁴⁾.

In the Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India, Sixty adults undergoing elective craniotomy for meningioma excision were randomized to receive either tranexamic acid or placebo, initiated prior to skin incision. Patients in the tranexamic acid group received an intravenous bolus of 20mg/kg over 20min followed by an infusion of 1mg/kg/h till the conclusion of surgery. Intraoperative blood loss, transfusion requirements, and estimating surgical hemostasis using a 5-grade scale were noted. Postoperatively, the extent of tumor excision on CT scan and complications were observed. Demographics, tumor characteristics, amount of fluid infusion, and duration of surgery and anesthesia were comparable between the two groups. The amount of blood loss was significantly less in the tranexamic acid group compared to the placebo (830mlvs 1124ml; p=0.03). The transfusion requirement was less in the tranexamic acid group (p>0.05). The patients in the tranexamic acid group fared better on a 5-grade surgical hemostasis scale with more patients showing good hemostasis (p=0.007). There were no significant differences between the groups regarding the extent of tumor removal, perioperative complications, hospital stay, or neurologic outcome. To conclude, the administration of tranexamic acid significantly reduced blood loss in patients undergoing excision of meningioma. Fewer patients in the tranexamic acid group received blood transfusions. Surgical field hemostasis was better achieved in patients who received tranexamic acid ⁵⁾.

A man in his 40s with a history of coronary artery disease previously treated with a drug-eluting stent presented for elective craniotomy and resection of an asymptomatic but enlarging meningioma. During his craniotomy, he received desmopressin and tranexamic acid for surgical bleeding. Postoperatively, the patient developed chest pain and was found to have an ST-elevation myocardial infarction (MI). Because of the patient’s recent neurosurgery, standard post-MI care was contraindicated and he was managed symptomatically in the intensive care unit. The echocardiogram on a postoperative day 1 demonstrated no regional wall motion abnormalities and an ejection fraction of 60%. His presentation was consistent with the thrombosis of his diagonal stent. He was transferred out of the intensive care unit on postoperative day 1 and discharged home on postoperative day 3 ⁶⁾.

Raghavendra et al. report the intraoperative use of tranexamic acid to secure complete hemostasis as a rescue measure in intracranial meningioma resection in uncontrollable bleeding ⁷⁾.

Three of 13 patients with intracranial meningiomas showed the pre-and postoperative elevation of tissue-type plasminogen activator (t-PA) related fibrinolytic activity in euglobulin fractions (EFA). During the operation, two of these three patients showed a significant elevation of the level of fibrinogen degradation products and oozing in the operating field. However, oozing was not observed in the third patient who had been given tranexamic acid preoperatively. Fibrin autography revealed that a broad lytic band of mol wt 50-60 kDa, probably free t-PA, appeared in the plasma obtained from two of the three patients after the operation when EFA elevated significantly. In all patients studied, the t-PA antigen levels were normal preoperatively but increased both during and after the operation, and correlated mainly with the intensities of a lytic band of mol wt 110 kDa, probably t-PA complexed with its major inhibitor (PAI-1). These results suggest that excessive fibrinolysis can induce local hemorrhagic diathesis during operation and may be related to t-PA function in plasma ⁸⁾.

¹⁾

Wijaya JH, July J, Quintero-Consuegra M, Chadid DP. A systematic review and meta-analysis of the effects of tranexamic acid in surgical procedure for intracranial meningioma. J Neurooncol. 2023 Jan 12. doi: 10.1007/s11060-023-04237-2. Epub ahead of print. PMID: 36633801.

²⁾

Li S, Yan X, Li R, Zhang X, Ma T, Zeng M, Dong J, Wang J, Liu X, Peng Y. Safety of intravenous tranexamic acid in patients undergoing supratentorial meningiomas resection: protocol for a randomized, parallel-group, placebo control, non-inferiority trial. BMJ Open. 2022 Feb 2;12(2):e052095. doi: 10.1136/bmjopen-2021-052095. PMID: 35110315; PMCID: PMC8811564.

³⁾

Rebai L, Mahfoudhi N, Fitouhi N, Daghmouri MA, Bahri K. Intraoperative tranexamic acid use in patients undergoing excision of intracranial meningioma: Randomized, placebo-controlled trial. Surg Neurol Int. 2021 Jun 14;12:289. doi: 10.25259/SNI_177_2021. PMID: 34221620; PMCID: PMC8247750.

⁴⁾

Ravi GK, Panda N, Ahluwalia J, Chauhan R, Singla N, Mahajan S. Effect of tranexamic acid on blood loss, coagulation profile, and quality of the surgical field in intracranial meningioma resection: A prospective randomized, double-blind, placebo-controlled study. Surg Neurol Int. 2021 Jun 7;12:272. doi: 10.25259/SNI_296_2021. PMID: 34221603; PMCID: PMC8247710.

⁵⁾

Hooda B, Chouhan RS, Rath GP, Bithal PK, Suri A, Lamsal R. Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma. J Clin Neurosci. 2017 Mar 7. pii: S0967-5868(16)31491-6. doi: 10.1016/j.jocn.2017.02.053. [Epub ahead of print] PubMed PMID: 28283245.

⁶⁾

Westfall KM, Ramcharan RN, Anderson HL 3rd. Myocardial infarction after craniotomy for asymptomatic meningioma. BMJ Case Rep. 2022 Dec 29;15(12):e252256. doi: 10.1136/bcr-2022-252256. PMID: 36581354; PMCID: PMC9806024.

⁷⁾

Raghavendra H, Varsha KS, Reddy MA, Kumar SS, Sunanda G, Nagarjuna T, Latha S. Rescue Measure in Giant Intracranial Meningioma Resection by Tranexamic Acid. J Neurosci Rural Pract. 2017 Aug;8(Suppl 1):S127-S129. doi: 10.4103/jnrp.jnrp_198_17. PMID: 28936089; PMCID: PMC5602238.

⁸⁾

Tsuda H, Oka K, Noutsuka Y, Sueishi K. Tissue-type plasminogen activator in patients with intracranial meningiomas. Thromb Haemost. 1988 Dec 22;60(3):508-13. PMID: 3149049.

Linezolid in Neurosurgery

December 18, 2022

Latest articles

Evidence for the effectiveness of linezolid in neurosurgical infections (NSIs) is growing. The comfortable oral dosage and tolerance of linezolid open the possibility for sequential antimicrobial treatment (SAT) in stable patients after a period of intravenous treatment ¹⁾.

Relevant studies were identified through searches of the PubMed, Current Contents, and Cochrane databases (publications archived until October 2006).

Case reports, case series, prospective and retrospective studies, and randomized controlled trials were eligible for inclusion in our review if they evaluated the effectiveness and safety of linezolid for the treatment of patients with CNS infections.

In 18 (42.9%) of the 42 relevant cases identified, patients had undergone neurosurgical operations and/or had prosthetic devices. Meningitis was the most common CNS infection, accounting for 20 (47.6%) cases. Other CNS infections included brain abscesses (14; 33.3%), ventriculitis (5; 11.9%), and ventriculo-peritoneal shunt infection (3; 7.1%). In the 39 patients in whom the responsible pathogen was isolated, those predominantly responsible for the CNS infections were: penicillin-nonsusceptible Streptococcus pneumoniae (7; 17.9%), vancomycin-resistant enterococci (6; 15.4%), Nocardia spp. (5; 12.8%), methicillin-resistant Staphylococcus epidermidis (4; 10.3%), and methicillin-resistant Staphylococcus aureus (3; 7.7%). Of the 42 patients who received linezolid for the treatment of CNS infections, 38 (90.5%) were either cured or showed clinical improvement of the infection. The mean duration of follow-up was 7.2 months; no recurrent CNS infection was reported.

The limited published data suggest that linezolid may be considered for the treatment of patients with CNS infections in cases of failure of previously administered treatment or limited available options ²⁾.

To evaluate the efficacy and safety of SAT with oral linezolid in patients with NSI and to analyse the cost implications, an observational, non-comparative, prospective cohort study was conducted on clinically stable consecutive adult patients at the Neurosurgical Service. Following intravenous treatment, patients were discharged with SAT with oral linezolid.

A total of 77 patients were included. The most common NSIs were: 41 surgical wound infections, 20 subdural empyemas, 18 epidural abscesses, and 16 brain abscesses. Forty-four percent of patients presented two or more concomitant NSIs. Aetiological agents commonly isolated were: Propionibacterium acnes (36 %), Staphylococcus aureus (23 %), Staphylococcus epidermidis (21 %) and Streptococcus spp. (13 %). The median duration of the SAT was 15 days (range, 3-42). The SAT was interrupted in five cases due to adverse events. The remainder of the patients were cured at the end of the SAT. A total of 1,163 days of hospitalisation were saved. An overall cost reduction of €516,188 was attributed to the SAT. Eight patients with device infections did not require removal of the device, with an additional cost reduction of €190,595. The mean cost saving per patient was €9,179.

SAT with linezolid was safe and effective for the treatment of NSI. SAT reduces hospitalisation times, which means significant savings of health and economic resources ³⁾.

Seventeen patients were included in the study. The main comorbidities among these patients included one or more of the following: subarachnoidal or intraventricular hemorrhage (n=8), solid neurological cancer (n=7), corticosteroids(n=9), and hydrocephalus (n=6). Eight patients underwent a craniotomy and fourteen patients had external ventricular drainage (EVD) as a predisposing factor for infection. Meningitis was the most common infection (11; 64.7%), followed by ventriculitis (4; 23.5%) and brain abscesses (2;11.8%). The main causative organisms were coagulase-negative Staphylococcus spp. (13; 76.5%). Linezolid was used as the initial therapy in 8 episodes, after therapy failure in 6, and for other reasons in 3. The oral route was used in 9 (52.9%) episodes; linezolid was initiated orally in 2 cases. The mean duration of treatment was 26.5 days (range 15-58). No adverse events were reported. Sixteen (94.1%) patients were considered cured. There was one recurrence. The mean length of hospital stay was 45.6 (range 15-112) days and the mean duration of follow-up was 7.2 (range 0.4-32) months. No related deaths occurred during active episodes.

Linezolid was mainly indicated in post-neurosurgical EVD-associated infections due to coagulase-negative Staphylococcus spp. It was used as initial therapy in most cases. A high rate of clinical cure was observed and no related adverse events were reported. More than half of the patients benefited from the advantages of the oral route of administration ⁴⁾.

In order to study the penetration of this antimicrobial into the cerebrospinal fluid (CSF) of such patients, the disposition of linezolid in serum and CSF was studied in 14 neurosurgical patients given linezolid at 600 mg twice daily (1-h intravenous infusion) for the treatment of CNS infections caused by gram-positive pathogens or for prophylactic chemotherapy. Serum and CSF linezolid steady-state concentrations were analyzed by high-pressure liquid chromatography, and the concentration-time profiles obtained were analyzed to estimate pharmacokinetic parameters. The mean +/- standard deviation (SD) linezolid maximum and minimum measured concentrations were 18.6 +/- 9.6 microg/ml and 5.6 +/- 5.0 microg/ml, respectively, in serum and 10.8 +/- 5.7 microg/ml and 6.1 +/- 4.2 microg/ml, respectively, in CSF. The mean +/- SD areas under the concentration-time curves (AUCs) were 128.7 +/- 83.9 microg x h/ml for serum and 101.6 +/- 59.6 microg x h/ml for CSF, with a mean penetration ratio for the AUC for CSF to the AUC for serum of 0.66. The mean elimination half-life of linezolid in CSF was longer than that in serum (19.1 +/- 19.0 h and 6.5 +/- 3.6 h, respectively). The serum and CSF linezolid concentrations exceeded the pharmacodynamic breakpoint of 4 microg/ml for susceptible target pathogens for the entire dosing interval in the majority of patients. These findings suggest that linezolid may achieve adequate concentrations in the CSF of patients requiring antibiotics for the management or prophylaxis of CNS infections caused by gram-positive pathogens ⁵⁾.

¹⁾

Jahoda D, Nyc O, Pokorný D, Landor I, Sosna A. [Linezolid in the treatment of antibiotic-resistant gram-positive infections of the musculoskeletal system]. Acta Chir Orthop Traumatol Cech. 2006 Oct;73(5):329-33. Czech. PubMed PMID: 17140514.

²⁾

Ntziora F, Falagas ME. Linezolid for the treatment of patients with central nervous system infection. Ann Pharmacother. 2007 Feb;41(2):296-308. Epub 2007 Feb 6. Review. PubMed PMID: 17284501.

³⁾

Martín-Gandul C, Mayorga-Buiza MJ, Castillo-Ojeda E, Gómez-Gómez MJ, Rivero-Garvía M, Gil-Navarro MV, Márquez-Rivas FJ, Jiménez-Mejías ME. Sequential antimicrobial treatment with linezolid for neurosurgical infections: efficacy, safety and cost study. Acta Neurochir (Wien). 2016 Oct;158(10):1837-43. doi: 10.1007/s00701-016-2915-0. Epub 2016 Aug 13. PubMed PMID: 27520361.

⁴⁾

Sousa D, Llinares P, Meijide H, Gutiérrez JM, Miguez E, Sánchez E, Castelo L, Mena A. Clinical experience with linezolid for the treatment of neurosurgical infections. Rev Esp Quimioter. 2011 Mar;24(1):42-7. PMID: 21412669.

⁵⁾

Myrianthefs P, Markantonis SL, Vlachos K, Anagnostaki M, Boutzouka E, Panidis D, Baltopoulos G. Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients. Antimicrob Agents Chemother. 2006 Dec;50(12):3971-6. doi: 10.1128/AAC.00051-06. Epub 2006 Sep 18. PMID: 16982782; PMCID: PMC1694012.

ShuntScope

December 1, 2022

Autoclavable reusable SHUNTSCOPE® is designed to facilitate the endoscopic ventricular drainage placement during shunt surgery.

A retrospective analysis of all pediatric patients undergoing ventricular catheter placement using the ShuntScope from 01/2012 to 01/2022 in the Department of Neurosurgery, Saarland University Medical Center, Homburg was performed. Demographic, clinical, and radiological data were evaluated. The visualization quality of the intraoperative endoscopy was stratified into the categories of excellent, medium, and poor and compared to the postoperative catheter tip placement. Follow-up evaluation included the surgical revision rate due to proximal catheter occlusion.

A total of 65 ShuntScope-assisted surgeries have been performed on 51 children. The mean age was 5.1 years. The most common underlying pathology was a tumor- or cyst-related hydrocephalus in 51%. Achieved image quality was excellent in 41.5%, medium in 43%, and poor in 15.5%. Ideal catheter placement was achieved in 77%. There were no intraoperative ventricular catheter placement complications and no technique-related morbidity associated with the ShuntScope. The revision rate due to proximal occlusion was 4.61% during a mean follow-up period of 39.7 years. No statistical correlation between image grade and accuracy of catheter position was observed (p-value was 0.290).

The ShuntScope can be considered a valuable addition to standard surgical tools in pediatric hydrocephalus treatment. Even suboptimal visualization contributes to high rates of correct catheter placement and, thereby, to a favorable clinical outcome ¹⁾.

The purpose of the study is to compare the accuracy of catheter placement and the complication and revision rates between SG and freehand (FH) techniques.

A retrospective study based on a prospectively acquired database of patients who underwent VC placement between September 2018 and July 2021. The accuracy of catheter placement was graded on postoperative imaging using a three-point Hayhurst grading system. Complication and revision rates were documented and compared between both groups with an average follow-up period of 20.84 months.

Results: Fifty-seven patients were included. SG technique was used in 29 patients (mean age was 6.3 years, 1.4 -27.7 years, 48.1% females), and FH technique was used in 28 patients (mean age was 26.7 years, 0.83 – 79.5 years, 67.9% female). The success rate for the optimal placement of the VC with a grade I on the Hayhurst scale was significantly higher in the SG group (93.1%) than in the FH group (60.7%), P = 0.012. The revision rate was higher in the FH group with 35.7% vs. 20.7% of in the SG group, P = 0.211.

Conclusion: VC placement using the SG technique is a safe and effective procedure, which enabled a significantly higher success rate and lower revision and complication rate. Accordingly, we recommend using the SG technique especially in patients with difficult anatomy ²⁾

The experience of shuntscope-guided ventriculoperitoneal shunt in 9 cases done from June 2015 to April 2016. Shuntscope is a 1 mm outer diameter semi-rigid scope from Karl Storz with 10000 pixels of magnification. It has a fiber optic lens system with a camera and light source attachment away from the scope to make it lightweight and easily maneuverable.

Results: In all cases, VC was placed in the ipsilateral frontal horn away from choroid plexuses, septae, or membranes. Septum pellucidum perforation and placement to the opposite side of the ventricle was identified with shunt scope assistance and corrected.

Conclusion: Although our initial results are encouraging, larger case series would be helpful. Complications and cost due to shunt dysfunction can thus be reduced to a great extent with shuntscope ³⁾

The semi-rigid ShuntScope (Karl Storz GmbH & Co.KG, Tuttlingen, Germany) with an outer diameter of 1.0 mm and an image resolution of 10,000 pixels was used in a series of 27 children and adolescents (18 males, 9 females, age range 2 months-18 years). Indications included catheter placement in aqueductal stenting (n = 4), first-time shunt placement (n = 5), burr hole reservoir insertion (n = 4), catheter placement after endoscopic procedures (n = 7) and revision surgery of the ventricle catheter (n = 7).

ShuntScope-guided precise catheter placement was achieved in 26 of 27 patients. In one case of aqueductal stenting, the procedure had to be abandoned. One single wound healing problem was noted as a complication. Intraventricular image quality was always sufficient to recognize the anatomical structures. In the case of catheter removal, it was helpful to identify adherent vessels or membranes. Penetration of small adhesions or thin membranes was feasible. Postoperative imaging studies demonstrated catheter tip placements analogous to the intraoperative findings.

Misplacements of shunt catheters are completely avoidable with the presented intra-catheter technique including slit ventricles or even aqueductal stenting. Potential complications can be avoided during revision surgery. The implementation of the ShuntScope is recommended in pediatric neurosurgery ⁴⁾.

Latest articles

¹⁾

Prajsnar-Borak A, Teping F, Oertel J. Image quality and related outcomes of the ShuntScope for catheter implantation in pediatric hydrocephalus-experience of 65 procedures. Childs Nerv Syst. 2022 Dec 2. doi: 10.1007/s00381-022-05776-1. Epub ahead of print. PMID: 36459211.

²⁾

Issa M, Nofal M, Miotik N, Seitz A, Unterberg A, El Damaty A. ShuntScope®-Guided Versus Free Hand Technique for Ventricular Catheter Placement: A Retrospective Comparative Study of Intra-Ventricular Catheter Tip Position and Complication Rate. J Neurol Surg A Cent Eur Neurosurg. 2022 Feb 10. doi: 10.1055/a-1768-3892. Epub ahead of print. PMID: 35144299.

³⁾

Agrawal V, Aher RB. Endoluminal Shuntscope-Guided Ventricular Catheter Placement: Early Experience. Asian J Neurosurg. 2018 Oct-Dec;13(4):1071-1073. doi: 10.4103/ajns.AJNS_98_17. PMID: 30459870; PMCID: PMC6208226.

⁴⁾

Senger S, Antes S, Salah M, Tschan C, Linsler S, Oertel J. The view through the ventricle catheter – The new ShuntScope for the therapy of pediatric hydrocephalus. J Clin Neurosci. 2018 Feb;48:196-202. doi: 10.1016/j.jocn.2017.10.046. Epub 2017 Nov 6. PubMed PMID: 29102235.

Stenotrophomonas maltophilia meningitis

September 1, 2022

Stenotrophomonas maltophilia treatment

The clinical characteristics of six Stenotrophomonas maltophilia ABM cases, collected during a study period of nine years (2001-2009) were included. In the related literature, 13 S. maltophilia ABM cases were reported, and their clinical data were also collected.

The 19 S. maltophilia ABM cases included 11 men and 8 women, aged 28-70 years. Of these 19 cases, 89.5% (17/19) had underlying neurosurgical (NS) conditions as the preceding event. Before the development of S. maltophilia ABM, 52.6% (10/19) of them had long stays in hospital and 63.2% (12/19) had undergone antibiotic treatment. Among the implicated S. maltophilia cases, three strains were found to have a resistance to sulfamethoxazole-trimethoprim (SMZ-TMP). Two of our five cases had resistant strains to levofloxacin. Among the antibiotics chosen for treatment, SMZ-TMP was the most common followed by quinolone (ciprofloxacin, levofloxacin, moxifloxacin). The therapeutic results showed 2 cases expired while the other 17 cases survived.

S. maltophilia ABM usually develops in patients with a preceding neurosurgical condition, a long hospital stay and antibiotic use. SMZ-TMP and quinolones, especially the ciprofloxacin, are the major antibiotic used. This study also shows the emergence of clinical S. maltophilia strains which are not susceptible to SMZ-TMP and quinolones and this development may pose a more serious threat in the near future because treatment options may become depleted and limited despite the mortality rate of this specific group of ABM not being high at this time ¹⁾.

A young female patient with history of multiple shunt revisions in the past, came with shunt dysfunction and exposure of the ventriculoperitoneal shunt tube in the neck. The abdominal end of the shunt tube was seen migrating into the bowel during shunt revision. The cerebrospinal fluid analysis showed evidence of Stenotrophomonas maltophilia growth. This is the first reported case of Stenotrophomonas maltophilia meningitis associated with ventriculoperitoneal shunt migration into the bowel. ²⁾.

A patient who developed C. utilis and S. maltophilia after undergoing neurosurgery and received effective nosocomial meningitis treatment. Multiple neurosurgeries were required for a 16-year-old girl due to complications. For probable nosocomial meningitis, she was treated with cefepime with vancomycin. Meropenem and liposomal amphotericin B were prescribed after her seizure and positive CSF culture for Candida utilis. Consequently, S. maltophilia was discovered in the CSF, and ceftazidime and trimethoprim-sulfamethoxazole were prescribed. The patient has been hemodynamically stable for the past two months, and consecutive CSF cultures have been negative. To the best of our knowledge, this is the first case of C. utilis and S. maltophilia co-infection that has been successfully handled. ³⁾.

Two cases of S. maltophilia meningitis following neurosurgical procedures. The first patient was a 60-year-old female. She was admitted to the hospital with a left basal ganglia bleed and underwent placement of an external ventricular drain for the treatment of hydrocephalus. She developed S. maltophilia meningitis 20 days after surgery. She was successfully treated with a combination of trimethoprim-sulfamethoxazole and intravenous colistin and the removal of the drain. She successfully underwent a ventriculoperitoneal (VP) shunt placement at the therapeutic midway point. The second patient was a 35-year-old male with a history of intracranial aneurysm bleeding. He had undergone a craniotomy and placement of a ventriculoperitoneal shunt two years previously. His shunt was replaced twice due to blockage. The last replacement had occurred 15 days prior to the development of meningitis. He was treated with a combination of trimethoprim-sulfamethoxazole and ceftazidime (as well as undergoing another shunt replacement) and experienced an excellent recovery. S. maltophilia is a rare but important cause of nosocomial meningitis. It is strongly associated with prior hospitalization and neurosurgical intervention, which is also found in our case series. The management of S. maltophilia meningitis is a therapeutic challenge due to its high resistance to multiple antibiotics. Optimal therapy is based on antimicrobial sensitivity, and the trimethoprim-sulfamethoxazole-based combination has been shown to be successful. The duration of therapy is debatable, but like most gram-negative meningitis infections, therapy lasting up to three weeks appears to be adequate. ⁴⁾.

Stenotrophomonas maltophilia CSF infection in infants after neurosurgery ⁵⁾.

A 4-year-old boy who developed meningitis associated with this organism, after several neurosurgical procedures and previous treatment with a broad-spectrum antibiotic. He was treated successfully with a combination of trimethoprim-sulfamethoxazole, ceftazidime and levofloxacin. Stenotrophomonas maltophilia should be considered as a potential cause of meningitis, especially among severely debilitated or immunosuppressed patients. Antimicrobial therapy is complicated by the high resistance of the organism to multiple antibiotics. ⁶⁾.

A case of a six months old, male child who developed meningitis caused by Stenotrophomonas maltophilia, after he underwent a neurosurgical procedure. ⁷⁾.

A 30-year-old male patient who developed meningitis associated with this organism after several neurosurgical procedures. A review of the literature revealed only 15 previous reports. Most cases were associated with neurosurgical procedures. Antimicrobial therapy is complicated by multiple drug resistance of the organism, and trimethoprim-sulfamethoxazole is the recommended agent for treatment. ⁸⁾.

A case of generalized infection by S. maltophilia, including meningitis, bacteremia and respiratory tract infection, in a patient who had undergone multiple neurosurgical procedures and who was treated with trimethoprim-sulphamethoxazole ⁹⁾.

Two cases of meningitis caused by Stenotrophomonas maltophilia in cancer patients following placement of an Ommaya reservoir for treatment of meningeal carcinomatosis. In addition, they review eight other cases of S. maltophilia that have been reported to date. Stenotrophomonas maltophilia meningitis is often associated with neurosurgical procedures; however, spontaneous infection may also occur, mainly in neonates. The disease’s clinical presentation is similar to that of other forms of meningitis caused by Gram-negative bacilli. The overall mortality rate of this disease is 20% and is limited to neonates with spontaneous meningitis in whom effective antibiotic therapy is delayed. Meningitis caused by S. maltophilia in the modern era should be considered in immunocompromised hosts with significant central nervous system disease who have undergone neurosurgical procedures and who do not readily respond to broad-spectrum antimicrobial coverage. ¹⁰⁾.

¹⁾

Huang CR, Chen SF, Tsai NW, Chang CC, Lu CH, Chuang YC, Chien CC, Chang WN. Clinical characteristics of Stenotrophomonas maltophilia meningitis in adults: a high incidence in patients with a postneurosurgical state, long hospital staying and antibiotic use. Clin Neurol Neurosurg. 2013 Sep;115(9):1709-15. doi: 10.1016/j.clineuro.2013.03.006. Epub 2013 Apr 20. PMID: 23611735.

²⁾

Manuel A, Jayachandran A, Harish S, Sunil T, K R VD, K R, Jo J, Unnikrishnan M, George K, Bahuleyan B. <i>Stenotrophomonas maltophilia</i> as a rare cause of meningitis and ventriculoperitoneal shunt infection. Access Microbiol. 2021 Oct 7;3(10):000266. doi: 10.1099/acmi.0.000266. PMID: 34816086; PMCID: PMC8604181.

³⁾

Mohzari Y, Al Musawa M, Asdaq SMB, Alattas M, Qutub M, Bamogaddam RF, Yamani A, Aldabbagh Y. Candida utilis and Stenotrophomonas maltophilia causing nosocomial meningitis following a neurosurgical procedure: A rare co-infection. J Infect Public Health. 2021 Nov;14(11):1715-1719. doi: 10.1016/j.jiph.2021.10.004. Epub 2021 Oct 13. PMID: 34700290.

⁴⁾

Khanum I, Ilyas A, Ali F. Stenotrophomonas maltophilia Meningitis – A Case Series and Review of the Literature. Cureus. 2020 Oct 28;12(10):e11221. doi: 10.7759/cureus.11221. PMID: 33269149; PMCID: PMC7704165.

⁵⁾

Mukherjee S, Zebian B, Chandler C, Pettorini B. Stenotrophomonas maltophilia CSF infection in infants after neurosurgery. Br J Hosp Med (Lond). 2017 Dec 2;78(12):724-725. doi: 10.12968/hmed.2017.78.12.724. PMID: 29240495.

⁶⁾

Correia CR, Ferreira ST, Nunes P. Stenotrophomonas maltophilia: rare cause of meningitis. Pediatr Int. 2014 Aug;56(4):e21-2. doi: 10.1111/ped.12352. PMID: 25252064.

⁷⁾

Sood S, Vaid VK, Bhartiya H. Meningitis due to Stenotrophomonas maltophilia after a Neurosurgical Procedure. J Clin Diagn Res. 2013 Aug;7(8):1696-7. doi: 10.7860/JCDR/2013/5614.3248. Epub 2013 Aug 1. PMID: 24086879; PMCID: PMC3782936.

⁸⁾

Yemisen M, Mete B, Tunali Y, Yentur E, Ozturk R. A meningitis case due to Stenotrophomonas maltophilia and review of the literature. Int J Infect Dis. 2008 Nov;12(6):e125-7. doi: 10.1016/j.ijid.2008.03.028. Epub 2008 Jun 24. PMID: 18579427.

⁹⁾

Platsouka E, Routsi C, Chalkis A, Dimitriadou E, Paniara O, Roussos C. Stenotrophomonas maltophilia meningitis, bacteremia and respiratory infection. Scand J Infect Dis. 2002;34(5):391-2. doi: 10.1080/00365540110080520. PMID: 12069028.

¹⁰⁾

Papadakis KA, Vartivarian SE, Vassilaki ME, Anaissie EJ. Stenotrophomonas maltophilia meningitis. Report of two cases and review of the literature. J Neurosurg. 1997 Jul;87(1):106-8. doi: 10.3171/jns.1997.87.1.0106. PMID: 9202275.

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