Prader–Willi syndrome

Prader–Willi syndrome

Prader–Willi syndrome (PWS) is a genetic disorder due to loss of function of specific genes.

In newborns, symptoms include weak muscles, poor feeding, and slow development.

Beginning in childhood, the person becomes constantly hungry, which often leads to obesity and type 2 diabetes.

Also, mild to moderate intellectual impairment and behavioral problems are typical.

Often, the forehead is narrow, hands and feet are small, height is short, skin is light in color, and most of the affected are unable to have children.

About 74% of cases occur when part of the father’s chromosome 15 is deleted.

In another 25% of cases, the person has two copies of chromosome 15 from their mother and none from their father.

As parts of the chromosome from the mother are turned off, they end up with no working copies of certain genes.

PWS is not generally inherited, but instead the genetic changes happen during the formation of the egg, sperm, or in early development.


Franco et al., presented case series from the Hospital das Clínicas. Four patients with genetically confirmed Prader-Willi syndrome (PWS) presenting with severe obesity were included.

Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months).

Primary outcome measures were adverse eventrecorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weightbody mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits.

Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking.

Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in the study, DBS was largely ineffective 1).


Lateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader-Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food-related cues induced an increase in beta/low-gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, Talakoub et al., delivered alpha-frequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity 2).

References

1)

Franco RR, Fonoff ET, Alvarenga PG, Alho EJL, Lopes AC, Hoexter MQ, Batistuzzo MC, Paiva RR, Taub A, Shavitt RG, Miguel EC, Teixeira MJ, Damiani D, Hamani C. Assessment of Safety and Outcome of Lateral Hypothalamic Deep Brain Stimulation for Obesity in a Small Series of Patients With Prader-Willi Syndrome. JAMA Netw Open. 2018 Nov 2;1(7):e185275. doi: 10.1001/jamanetworkopen.2018.5275. PubMed PMID: 30646396.
2)

Talakoub O, Paiva RR, Milosevic M, Hoexter MQ, Franco R, Alho E, Navarro J, Pereira JF Jr, Popovic MR, Savage C, Lopes AC, Alvarenga P, Damiani D, Teixeira MJ, Miguel EC, Fonoff ET, Batistuzzo MC, Hamani C. Lateral hypothalamic activity indicates hunger and satiety states in humans. Ann Clin Transl Neurol. 2017 Oct 20;4(12):897-901. doi: 10.1002/acn3.466. eCollection 2017 Dec. PubMed PMID: 29296618; PubMed Central PMCID: PMC5740250.

Dravet Syndrome

Dravet syndrome, previously known as severe myoclonic epilepsy of infancy (SMEI), is a type of epilepsy with seizures that are often triggered by hot temperatures or fever.

Dravet and Bureau in 1981 described “benign myoclonic epilepsy in infancy” in 7 normal children with onset of myoclonic seizures in the first 3 years of life 1). The syndrome was defined as including myoclonic seizures only, except rare simple febrile seizures, with good prognosis regarding response to therapy and cognitive functions.

Dravet Syndrome (DS) is a severe epileptic encephalopathy of childhood involving intractable seizures, recurrent status epilepticus and cognitive decline. Because DS is a rare disease, available data is limited and evidence-based treatment guidelines are lacking.

Both VNS and corpus callosotomy (CC) can be effective at reducing seizure frequency. Patients with DS may benefit from earlier and more aggressive surgical intervention. Studies using larger patient cohorts will help clarify the role that surgery may play in the multidisciplinary approach to controlling seizures in DS. Further studies will help determine the appropriate timing of and type of surgical intervention 2).

Loss of function in the Scn1a gene leads to Dravet syndrome (DS). Reduced excitability in cortical inhibitory neurons is thought to be the major cause of DS seizures.

Ritter-Makinson et al., showed enhanced excitability in thalamic inhibitory neurons that promotes the non-convulsive seizures that are a prominent yet poorly understood feature of DS. In a mouse model of DS with a loss of function in Scn1a, reticular thalamic cells exhibited abnormally long bursts of firing caused by the downregulation of calcium-activated potassium SK channels. The study supports a mechanism in which loss of SK activity causes the reticular thalamic neurons to become hyperexcitable and promote non-convulsive seizures in DS. They propose that reduced excitability of inhibitory neurons is not global in DS and that non-GABAergic mechanisms such as SK channels may be important targets for treatment 3).


Vagus nerve stimulation (VNS) is an established neurostimulation treatment for intractable epilepsy, however little evidence is published on its efficacy in patients with DS.

Dibué-Adjei et al., performed a meta-analysis of all peer-reviewed English language studies reporting seizure outcomes of patients with DS treated with adjunctive vagus nerve stimulation. The primary and secondary outcome measures were ≥50% reduction of seizures or of the most-debilitating seizure type and seizure reduction per patient.

13 studies comprising 68 patients met the inclusion criteria of which 11 were single-center retrospective case series, one was a multi-center retrospective analysis and one was a case report. 52.9% of patients experienced a ≥50% reduction of seizures and the average seizure reduction, which could only be assessed in n=28 patients was 50.8%. 7 out of 13 studies reported additional benefits of VNS, however this could not be assessed systematically.

Vagus nerve stimulation appears to reduce seizure frequency in patients with DS. Based on this preliminary analysis, controlled trials of VNS in this rare condition using patient-centric outcome measures are indicated 4).

1)

Dravet C, Bureau M. [The benign myoclonic epilepsy of infancy (author’s transl)]. Rev Electroencephalogr Neurophysiol Clin. 1981 Dec;11(3-4):438-44. French. PubMed PMID: 6808601.
2)

Dlouhy BJ, Miller B, Jeong A, Bertrand ME, Limbrick DD Jr, Smyth MD. Palliative epilepsy surgery in Dravet syndrome-case series and review of the literature. Childs Nerv Syst. 2016 Sep;32(9):1703-8. doi: 10.1007/s00381-016-3201-4. Epub 2016 Jul 27. Review. PubMed PMID: 27465677.
3)

Ritter-Makinson S, Clemente-Perez A, Higashikubo B, Cho FS, Holden SS, Bennett E, Chkaidze A, Eelkman Rooda OHJ, Cornet MC, Hoebeek FE, Yamakawa K, Cilio MR, Delord B, Paz JT. Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome. Cell Rep. 2019 Jan 2;26(1):54-64.e6. doi: 10.1016/j.celrep.2018.12.018. PubMed PMID: 30605686.
4)

Dibué-Adjei M, Fischer I, Steiger HJ, Kamp MA. Efficacy of adjunctive vagus nerve stimulation in patients with Dravet syndrome: A meta-analysis of 68 patients. Seizure. 2017 Aug;50:147-152. doi: 10.1016/j.seizure.2017.06.007. Epub 2017 Jun 17. Review. PubMed PMID: 28666193.

Cyclic Cushing’s syndrome

Cyclic Cushing’s syndrome is a rare variant of Cushing’s syndrome, which demonstrates periodic cortisol excess.

Cyclical Cushing’s syndrome may render the diagnosis and management of Cushing’s disease difficult.

It has been suspected that inhibition of a glucocorticoid positive feedback loop is associated with remission of hypercortisolism in ACTH-dependent cyclic Cushing’s syndrome. However, the underlying mechanism to trigger the development of its hypercortisolism is still unknown.

Seki et al., from the Tokyo Women’s Medical University, experienced a case of ACTH-dependent cyclic Cushing’s syndrome developed by exogenous glucocorticoids possibly through a glucocorticoid positive-feedback loop.

A 75-year-old woman had experienced cyclic ACTH and cortisol elevations 6 times in the previous 4 years. Her diagnosis was cyclic Cushing’s syndrome. During the hypercortisolemic phase, neither low-dose nor high-dose dexamethasone suppressed her plasma ACTH and cortisol levels. Daily metyraponetherapy decreased her plasma cortisol and ACTH levels during every hypercortisolemic phase. After the sixth remission of a hypercortisolemic phase, she took 25 mg hydrocortisone for 4 weeks and developed ACTH-dependent hypercortisolemia. Treatment with 1 mg dexamethasone gradually increased both plasma ACTH and cortisol levels over 2 weeks resulting in the eighth hypercortisolemic phase. Treatment using a combination of dexamethasone with metyrapone did not increase plasma ACTH or cortisol levels and successfully prevented development of ACTH-dependent hypercortisolism.

It is an interesting case of cyclic Cushing’s syndrome in which ACTH-dependent hypercortisolemic phases relapsed during exogenous glucocorticoid treatment. A glucocorticoid positive-feedback loop and endogenous glucocorticoid synthesis may play key roles in the periodicity of hypercortisolism in cyclic Cushing’s syndrome 1).


Alexandraki et al., analysed the case records of 201 patients with Cushing’s disease in a retrospective case-note study. Cyclicity was considered as the presence of at least one cycle, defined as a clinical and/or biochemical hypercortisolaemic peak followed by clinical and biochemical remission, followed by a new clinical and/or biochemical hypercortisolaemic peak. The fluctuations of mean serum cortisol levels, as assessed by a 5-point cortisol day curve, defined the variability.

Thirty (14.9%; 26 females) patients had evidence of cyclicity/variability. ‘Cycling’ patients were older but no difference in sex or paediatric distribution was revealed between ‘cycling’ and ‘non-cycling’ patients. The median number of cycles was two for each patient, and 4 years was the median intercyclic period. A trend to lower cure rate post-neurosurgery and lower adenoma identification was observed in ‘cycling’ compared with ‘non-cycling’ patients. In multivariate analysis, older patients, longer follow-up, female sex and no histological identification of the adenoma were associated with an increased risk of cyclic disease.

This large population study reveals that cyclicity/variability is not an infrequent phenomenon in patients with Cushing’s disease, with a minimum prevalence of 15%. Physicians should be alert since it can lead to frequent problems in diagnosis and management, and no specific features can be used as markers 2).


A 56-year-old male patient with cyclic Cushing’s disease remained in a state of remission for more than one year with a relatively low dose of bromocriptine (2.5-3.75 mg/day). It has been reported that bromocriptine treatment for cyclic Cushing’s disease induces only a transient remission; in the most effective cases, a relatively high dose (40 mg/day) was necessary. In the hypercortisolemic state, plasma adrenocorticotropic hormone (ACTH) and serum cortisol were not suppressed by dexamethasone and did not respond to corticotropin-releasing factor (CRF). An antehypophysectomy was not effective, even though the resected tissue contained ACTH-positive microadenomas. The present observations thus indicate the effectiveness of bromocriptine for some patients with this rare disorder 3).


A cyclic excess of cortisol secretion was detected in a patient with diabetes insipidus and diabetes mellitus. The cycles of hypercortisolism were of 7 days’ duration, but during the nadir of these cycles urinary excretion of corticosteroids and 17-ketosteroids was within the normal range. The radiological appearance of the sella turcica was normal; however, computerized axial tomography of the head revealed a small tumor immediately superior to the sella turcica. At operation a small chromophobe adenoma superior to the diaphragma sellae and involving the hypophysial stalk was partially resected. Postoperatively, the patient continued to have 7-day cycles of increased corticosteroid excretion, but the amounts excreted were less than they had been preoperatively. Other patients have been described in whom Cushing’s disease has been due to cyclic hypercortisolism. These cycles have been remarkably regular in individual patients, but of variable duration in different patients. Furthermore, cyclic hormonogenesis probably occurs in a variety of endocrinopathies 4).

References

1)

Seki Y, Morimoto S, Saito F, Takano N, Kimura S, Yamashita K, Yoshida N, Bokuda K, Sasaki N, Yatabe M, Watanabe D, Yatabe J, Ando T, Amano K, Kawamata T, Ichihara A. ACTH-dependent Cyclic Cushing’s Syndrome Triggered by Glucocorticoid Excess Through a Positive-Feedback Mechanism. J Clin Endocrinol Metab. 2018 Dec 17. doi: 10.1210/jc.2018-02268. [Epub ahead of print] PubMed PMID: 30561712.
2)

Alexandraki KI, Kaltsas GA, Isidori AM, Akker SA, Drake WM, Chew SL, Monson JP, Besser GM, Grossman AB. The prevalence and characteristic features of cyclicity and variability in Cushing’s disease. Eur J Endocrinol. 2009 Jun;160(6):1011-8. doi: 10.1530/EJE-09-0046. Epub 2009 Mar 16. PubMed PMID: 19289537.
3)

Adachi M, Takayanagi R, Yanase T, Sakai Y, Ikuyama S, Nakagaki H, Osamura Y, Sanno N, Nawata H. Cyclic Cushing’s disease in long-term remission with a daily low dose of bromocriptine. Intern Med. 1996 Mar;35(3):207-11. PubMed PMID: 8785455.
4)

Oates TW, McCourt JP, Friedman WA, Agee OF, Rhoton AL, Thomas WC Jr. Cushing’s disease with cyclic hormonogenesis and diabetes insipidus. Neurosurgery. 1979 Nov;5(5):598-603. PubMed PMID: 534067.

Loin Pain Hematuria Syndrome

Loin Pain Hematuria Syndrome (LPHS) is a rare condition characterized by cryptogenic debilitating flank pain and microscopic or macroscopic hematuria.

Pathophysiology

The pathophysiology of LPHS remains poorly understood and diagnosis is made largely by exclusion of alternate pathology.

Treatment

Management strategies can vary widely and include chronic opioid medication and a variety of invasive procedures including regional nerve blocks, transcutaneous electrical nerve stimulation, local capsaicin infusion, and surgical renal denervation. Neuromodulation may provide a new paradigm of treatment for LPHS, potentially sparing patients from long term complications of opiate therapy and invasive surgery.

A report of Richter et al. from the Department of Neurosurgery, Allegheny General Hospital, demonstrates the first case of successful symptomatic management of LPHS using spinal cord stimulation1).

1) Richter B, Bergman J, Pierre J, Tomycz ND. Spinal Cord Stimulation for LoinPain Hematuria Syndrome: Case Report. Pain Pract. 2018 Dec 16. doi:10.1111/papr.12755. [Epub ahead of print] PubMed PMID: 30554461.

UpToDate: Mohr-Tranebjaerg Syndrome

Mohr-Tranebjaerg Syndrome

Deafnessdystoniaoptic neuronopathy (DDON) syndrome, also known as Mohr-Tranebjærg syndrome, is characterized by hearing loss that begins early in life, problems with movement, impaired vision, and behaviorproblems. This condition occurs almost exclusively in males.

Case reports

Coenen et al. from the Department of Stereotactic and Functional Neurosurgery, Department of Neurology and Neurophysiology, Department of Neuroradiology, University Hospital Freiburg and Parkinson-Klinik Wolfach, Germany, reported a 28-year-old man presented with a history of sensorineural deafness since early childhood treated with bilateral cochlear implants (CIs). He showed signs of debilitating dystonia that had been present since puberty. Dystonic symptoms, especially a protrusion of the tongue and bilateral hand tremor, had not responded to botulinum toxin therapy. They diagnosed Mohr-Tranebjaerg syndrome (MTS).

Deep brain stimulation (DBS) of the bilateral globus pallidus internus was performed predominantly with stereotaxic computed tomography angiography guidance under general anesthesiaElectrophysiology was used to identify the target regions and to guide DBS electrode placement.

In the immediate postoperative course and stimulation, the patient showed marked improvement of facial, extremity, and cervical dystonia. More than 2 years after implantation, his dystonic symptoms had dramatically improved by 82%.

The use of DBS for the dystonia in MTS was previously described but not in the presence of bilateral CIs.

DBS in MTS may be a viable option to treat debilitating dystonic symptoms. They describe successful DBS surgery, despite the presence of bilateral CIs, and stimulation therapy over 2 years 1).


Eggink et al. from the Department of Neurology, Department of Genetics, Department of Rehabilitation, Department of Neurosurgery, University Medical Center Groningen, The Netherlands, reported two patients with dystonia-deafness syndrome due to a beta-actin gene mutation.

They report on disease course, genetic testing, and management of 2 patients, mother and daughter, presenting with dystonia-deafness syndrome.

After exclusion of known dystonia-deafness syndrome causes, whole-exome sequencing revealed a beta-actin gene mutation (p.Arg183Trp) in both patients. Although beta-actin gene mutations are generally associated with developmental Baraitser-Winter syndrome, dystonia-deafness syndrome has been reported once in identical twin brothers. Bilateral GPi-DBS led to a significant decrease of dystonia and regain of independency in our patients.

The p.Arg183Trp mutation in the beta-actin gene is associated with the clinical presentation of dystonia-deafness syndrome, even with only minimal or no developmental abnormalities of Baraitser-Winter syndrome. GPi-DBS should be considered to ameliorate the invalidating dystonia in these patients. 2).


Cif et al. reported in 2013 the article Progressive dystonia in Mohr-Tranebjaerg syndrome with cochlear implant and deep brain stimulation 3).

References

1)

Coenen VA, Rijntjes M, Sajonz B, Piroth T, Prokop T, Jost W, Trippel M, Urbach H, Reinacher PC. Bilateral Globus Pallidus Internus Deep Brain Stimulation in a Case of Progressive Dystonia in Mohr-Tranebjaerg Syndrome with Bilateral Cochlear Implants. J Neurol Surg A Cent Eur Neurosurg. 2018 Oct 5. doi: 10.1055/s-0038-1669472. [Epub ahead of print] PubMed PMID: 30290379.

2)

Eggink H, van Egmond ME, Verschuuren-Bemelmans CC, Schönherr MC, de Koning TJ, Oterdoom DL, van Dijk JM, Tijssen MA. Dystonia-deafness syndrome caused by a β-actin gene mutation and response to deep brain stimulation. Mov Disord. 2017 Jan;32(1):162-165. doi: 10.1002/mds.26842. Epub 2016 Nov 8. PubMed PMID: 27862284.

3)

Cif L, Gonzalez V, Garcia-Ptacek S, James S, Boetto J, Seychelles A, Roujeau T, Moura De Ribeiro AM, Sillon M, Mondain M, Coubes P. Progressive dystonia in Mohr-Tranebjaerg syndrome with cochlear implant and deep brain stimulation. Mov Disord. 2013 Jun;28(6):737-8. doi: 10.1002/mds.25519. PubMed PMID: 23801560.

UpToDate: Shunt dependency syndrome

Shunt dependency syndrome

Intraventricular hemorrhage (IVH) is a common affliction of preterm infants and often results in posthemorrhagic hydrocephalus (PHH). These patients typically eventually require permanent CSF diversion and are presumed to be indefinitely shunt-dependent.

In a cohort of patients with clinical grade aneurysmal subarachnoid hemorrhage (aSAH) at admission, larger amounts of subarachnoid blood and large ventricular size on preoperative cerebral CT, and CSF drainage in excess of 1,500 ml during the 1st week after the ictus were significant predictors of shunt dependency. Shunt dependency did not hamper outcome 1).

Aneurysmal subarachnoid hemorrhage (SAH) has been reported to induce an intrathecal inflammatory reaction reflected by cytokine release, particularly interleukin 6 (IL-6), which correlates with early brain damage and poor outcome.

CSF IL-6 values of ≥10,000 pg/ml in the early post-SAH period may be a useful diagnostic tool for predicting shunt dependency in patients with acute posthemorrhagic hydrocephalus. The development of shunt-dependent posthemorrhagic hydrocephalus remains a multifactorial process 2).

Graeb Score or LeRoux scores improve the prediction of shunt dependency and in parts of case fatality rate (CFR) in aneurysmal SAH patients therefore confirming the relevance of the extent and distribution of intraventricular hemorrhage for the clinical course in SAH 3).

A significantly higher rate of shunt dependency was observed for age older than 65 years, poor initial neurological status, and thick SAH with presence of initial intraventricular hemorrhage. By understanding these factors related to development of SDHC and results, it is expected that management of aneurysmal SAH will result in a better prognosis 4).

In a study SD after aSAH showed no correlations with three of the parameters previously identified as risk factors for shunt dependent hydrocephalus, namely, the amount of SAH, the presence of IVH, or acute hydrocephalus. Instead, a longer duration of CSF drainage correlated with SD as an independent factor. These data suggest that a longer duration of CSF drainage may be one of the risk factors for SD after aSAH 5).

Case series

2015

A total of 471 patients who were part of the Barrow Ruptured Aneurysm Trial (BRAT) from 2003 to 2007 were retrospectively reviewed. All variables including demographic data, medical history, treatment, imaging, and functional outcomes were included as part of the trial. No additional variables were retrospectively collected.

Ultimately, 147 patients (31.2%) required a ventriculoperitoneal shunt (VPS) in this series. Age, dissecting aneurysm type, ruptured vertebrobasilar aneurysm, Fisher grade, Hunt and Hess grade, admission intraventricular hemorrhage, admission intraparenchymal hemorrhage, blood in the fourth ventricle on admission, perioperative ventriculostomy, and hemicraniectomy were significant risk factors (P < .05) associated with shunt-dependent hydrocephalus on univariate analysis. On multivariate analysis, intraventricular hemorrhage and intraparenchymal hemorrhage were independent risk factors for shunt dependency (P < .05). Clipping vs coiling treatment was not statistically associated with VPS after SAH on both univariate and multivariate analyses. Patients who did not receive a VPS at discharge had higher Glasgow Outcome Scale and Barthel Index scores and were more likely to be functionally independent and to return to work 72 months after surgery (P < .05).

There is no difference in shunt dependency after SAH among patients treated by endovascular or microsurgical means. Patients in whom shunt-dependent hydrocephalus does not develop after SAH tend to have improved long-term functional outcomes 6).


Wang et al. analyzed retrospectively collected data for 89 preterm patients diagnosed with grades III and IV IVH and PHH from 1998 to 2011.

Sixty-nine out of 89 patients (77.5 %) underwent ventriculoperitoneal shunt placement, and 33 (47.8 %) required at least one shunt revision and 18 (26.1 %) required multiple revisions. The mean ± standard deviation follow-up time for shunted patients was 5.0 ± 3.3 years. The majority of early failures were due to proximal catheter malfunction, while later failures were mostly due to distal catheter problems. There was a significant difference in the number of patients requiring revisions in the first 3 years following initial VP shunt insertion compared after 3 years, with 28 revisions versus 10 (p < 0.004). In 8 out of 10 patients who underwent shunt revisions after 3 years, evidence of obstructive hydrocephalus was found on imaging either in the form of an isolated fourth ventricular cyst or aqueductal stenosis.

The results suggest that in a distinct subset of patients with PHH, obstructive hydrocephalus may develop, resulting in long-term dependence on CSF diversion. Further study on the factors associated with long-term shunt dependence and revision requirements within the PHH group is warranted 7).

2014

88 consecutive patients with aneurysmal SAH requiring external ventricular drain placement and endovascular aneurysm closure were included. Functional outcome and shunt dependency were assessed 90 days after event. A matched controlled sub-analysis was carried out to investigate the effects of IVF treatment (n = 14; matching criteria: age, neuro-status and imaging). Multivariate modeling was performed to identify independent predictors for permanent shunt dependency.

In IVF-patients neurological status was significantly poorer [Hunt&Hess: IVF = 4(3-5) vs. non-IVF = 3(1-5); p = 0.035] and the extent of ventricular hemorrhage was increased [Graeb Score: IVF = 7(6-8) vs. non-IVF = 3(1-4); p ≤ 0.001]. Consecutive matched controlled sub-analysis revealed no significant therapeutic effect of IVF with respect to shunt dependency rate and functional outcome. Multivariate analysis revealed Graeb score [OR = 1.34(1.02-1.76); p = 0.035] and sepsis [OR = 11.23(2.28-55.27); p = 0.003] as independent predictors for shunt dependency, whereas IVF did not exert significant effects (p = 0.820).

In endovascular-treated SAH patients IVF neither reduced permanent shunt dependency nor influenced functional outcome. Despite established effects on intraventricular clot resolution IVF appears less powerful in SAH as compared to ICH. Given the reported positive effects of lumbar drainage (LD) in SAH, a prospective analysis of a combined treatment approach of IVF and subsequent lumbar drain sOeems warranted aiming to reduce permanent shunting and improve functional outcome 8).

1999

Of 138 patients treated for ruptured aneurysms the development of shunt dependent hydrocephalus was evaluated regarding possible predictive factors. In 15 patients (11%) ventriculo-atrial shunt was implanted due to hydrocephalus. One predictive factor was the localisation of aneurysms as patients with hydrocephalus had PcoA aneurysms in 40% compared to 20% in the group of patients without hydrocephalus and only 7% compared to 28% MCA aneurysms. An other predictive factor was the severity of the subarachnoid haemorrhage (SAH) as 7 patients out of the 15 were graded Fisher IV on admission. Furthermore, an important predictive factor was the presence of acute hydrocephalus as 13 out of the 15 patients (87%) with shunt dependent hydrocephalus had acute hydrocephalus requiring external ventricular drainage. An other possible factor was the intraoperative opening of the lamina terminalis as in 73% of the patients with shunt dependent hydrocephalus compared to 82% in the group of patients without hydrocephalus this procedure was performed during surgery. The results suggest that shunt dependency is more likely after severe SAH especially in the presence of an acute hydrocephalus and in patients with aneurysms located in the basal cisterns. Therefore treatment of the acute hydrocephalus and possible the opening of the lamina terminalis could have a positive effect on the development of shunt dependent hydrocephalus after SAH 9).

1979

Five patients with shunt dependency were observed to have apparently normal ventricular size despite marked increases in ventricular pressure after shunt malfunctionElastance (dP/dV) was determined in four of these patients by removing increments of cerebrospinal fluid and measuring the resulting pressure. These patients without ventricular enlargement and with markedly increased ventricular pressure had high elastance. This group of patients with “normal volume” hydrocephalus had distal shunt occlusions, in contrast to previously reported patients with cephalic shunt obstructions after ventricular decompression. Initial shunting in early infancy, prolonged shunt dependency, and lack of recent shunt revision were common factors in these patients. Markedly elevated pressure with normal volume is a threatening clinical entity, requiring prompt surgical intervention 10).

1975

In suitable cases, intermittent cranial compression by means of an elastic bandage or a helmet with an inflatable inner-lining may be effective. There was arrested hydrocephalus in nine of 14 children treated with this method, eight of whom have developed normally. When cranial compression is contra-indicated or not successful, the preferred method of treatment is an ‘on-off’ type of valve which is used intermittently to drain a fixed volume of cerebrospinal fluid. Of 18 children who had such shunts inserted, 10 have become totally independent of their shunts and their hydrocephalus has become compensated. All are of normal intelligence. Subtemporal craniectomy was performed on seven shunt-dependent children with recurrent catheter obstruction. Four have been followed for six months and three for two years and in no case has there been further malfunction of the proximal catheter 11).

Case reports

Dong et al., from the Tongji Hospital, Huazhong University of Science and Technology, WuhanChina report two children with middle fossa arachnoid cysts who underwent cystoperitoneal shunt with fixed pressure valve at an opening pressure of 7 cmH2O and then developed dependency syndrome. Both patients were effectively treated by mini-invasive cyst wall excision with the shunts reserved. The clinical manifestation, radiological findings, treatment methods, and therapeutic outcomes were reviewed retrospectively.

The time from shunt surgery to shunt dependency syndrome occurrence was 4 and 2 years, respectively. Computed tomography/magnetic resonance findings of the brain showed remarkably collapsed cysts with normal or small ventricles. Both patients underwent secondary mini-invasive cyst wall excision and shunt catheters were reserved. After the operations, their symptoms were resolved except one case with marginally improved visual impairment.

Shunt dependency syndrome is a rare but dangerous complication of CP shunt and should be treated in time. Collapsed and thickened cyst wall intermittent covering the catheter head end, decreased brain compliance due to chronic fibrosis, as well as regression of cerebrospinal fluidabsorption could be the pathogenesis. They suggest keyhole resection of the residual cyst wall as an effective and mini-invasive treatment option12).


Sonobe et al. report two cases of high shunt dependency, which were first thought to be shunt independent arrested hydrocephalus. Though their shunt systems didn’t seem to work, symptoms of rapid increasing intracranial pressure were observed after obstruction or replacement of shunt tube. Their ventricles looked so small like a slit on CT scan and PVG that the apex of the ventricular tube were easily obstructed by a ventricle wall. This is the reason why we misjudged them to be shunt independent arrested hydrocephalus. The cause of slit-like ventricles was overflow of CSF fluid due to the low pressure valve and the siphon effect. In general, after the shunt operation, most of the cases with thickening of cerebral mantle show the shunt dependency. Especially the cases showing rapid and marked thickening of the cerebral mantle are highly shunt dependent. Therefore, we must observe such cases carefully, in which the ventricle becomes small. Short interval follow-ups by CT scan after the shunt operation are quite necessary in order to observe the ventricle size. Easy and reliable judging method to know whether the shunt system is working or not is required to be developed 13).

References

1)

Erixon HO, Sorteberg A, Sorteberg W, Eide PK. Predictors of shunt dependency after aneurysmal subarachnoid hemorrhage: results of a single-center clinical trial. Acta Neurochir (Wien). 2014 Nov;156(11):2059-69. doi: 10.1007/s00701-014-2200-z. Epub 2014 Aug 22. PubMed PMID: 25143185.
2)

Wostrack M, Reeb T, Martin J, Kehl V, Shiban E, Preuss A, Ringel F, Meyer B, Ryang YM. Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage: The Role of Intrathecal Interleukin-6. Neurocrit Care. 2014 May 20. [Epub ahead of print] PubMed PMID: 24840896.
3)

Czorlich P, Ricklefs F, Reitz M, Vettorazzi E, Abboud T, Regelsberger J, Westphal M, Schmidt NO. Impact of intraventricular hemorrhage measured by Graeb and LeRoux score on case fatality risk and chronic hydrocephalus in aneurysmal subarachnoid hemorrhage. Acta Neurochir (Wien). 2015 Mar;157(3):409-15. doi: 10.1007/s00701-014-2334-z. Epub 2015 Jan 21. PubMed PMID: 25599911.
4)

Bae IS, Yi HJ, Choi KS, Chun HJ. Comparison of Incidence and Risk Factors for Shunt-dependent Hydrocephalus in Aneurysmal Subarachnoid Hemorrhage Patients. J Cerebrovasc Endovasc Neurosurg. 2014 Jun;16(2):78-84. doi: 10.7461/jcen.2014.16.2.78. Epub 2014 Jun 30. PubMed PMID: 25045646; PubMed Central PMCID: PMC4102754.
5)

Sugawara T, Maehara T, Tadashi N, Aoyagi M, Ohno K. Independent predictors of shunt-dependent normal pressure hydrocephalus after aneurysmal subarachnoid hemorrhage. J Neurosurg Sci. 2014 Jul 29. [Epub ahead of print] PubMed PMID: 25069541.
6)

Zaidi HA, Montoure A, Elhadi A, Nakaji P, McDougall CG, Albuquerque FC, Spetzler RF, Zabramski JM. Long-term functional outcomes and predictors of shunt-dependent hydrocephalus after treatment of ruptured intracranial aneurysms in the BRAT trial: revisiting the clip vs coil debate. Neurosurgery. 2015 May;76(5):608-13; discussion 613-4; quiz 614. doi: 10.1227/NEU.0000000000000677. PubMed PMID: 25714521.
7)

Wang JY, Jackson EM, Jallo GI, Ahn ES. Shunt revision requirements after posthemorrhagic hydrocephalus of prematurity: insight into the time course of shunt dependency. Childs Nerv Syst. 2015 Nov;31(11):2123-30. doi: 10.1007/s00381-015-2865-5. Epub 2015 Aug 7. PubMed PMID: 26248674.
8)

Gerner ST, Kuramatsu JB, Abel H, Kloska SP, Lücking H, Eyüpoglu IY, Doerfler A, Schwab S, Huttner HB. Intraventricular fibrinolysis has no effects on shunt dependency and functional outcome in endovascular-treated aneurysmal SAH. Neurocrit Care. 2014 Dec;21(3):435-43. doi: 10.1007/s12028-014-9961-3. PubMed PMID: 24566979.
9)

Schmieder K, Koch R, Lücke S, Harders A. Factors influencing shunt dependency after aneurysmal subarachnoid haemorrhage. Zentralbl Neurochir. 1999;60(3):133-40. PubMed PMID: 10726336.
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Engel M, Carmel PW, Chutorian AM. Increased intraventricular pressure without ventriculomegaly in children with shunts: “normal volume” hydrocephalus. Neurosurgery. 1979 Nov;5(5):549-52. PubMed PMID: 534062.
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Epstein FJ, Hochwald GM, Wald A, Ransohoff J. Avoidance of shunt dependency in hydrocephalus. Dev Med Child Neurol Suppl. 1975;(35):71-7. PubMed PMID: 812752.
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Dong F, Wang Z, Li Y, Chen Z, Zhang S, Wan F. Shunt Dependency Syndrome after Cyst-Peritoneal Shunt Resolved by Keyhole Microsurgical Cyst Resection: Two Case Reports and Literature Review. Neuropediatrics. 2018 Jul 12. doi: 10.1055/s-0038-1661395. [Epub ahead of print] PubMed PMID: 30001565.
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Sonobe M, Kodama N, Fujiwara S, Takaku A, Suzuki J. [On-off mechanism of shunt system due to slit ventricle (author’s transl)]. No Shinkei Geka. 1978 Dec;6(12):1193-6. Japanese. PubMed PMID: 732936.

UpToDate: Tourette syndrome

Tourette syndrome

Tourette syndrome (also called Tourette’s syndrome, Tourette’s disorder, Gilles de la Tourette syndrome, GTS or, more commonly, simply Tourette’s or TS) is an inherited neuropsychiatric disorder with onset in childhood, characterized by multiple physical (motor) tics and at least one vocal (phonic) tic. These tics characteristically wax and wane, can be suppressed temporarily, and are preceded by a premonitory urge. Tourette’s is defined as part of a spectrum of tic disorders, which includes provisional, transient and persistent (chronic) tics.

Tourette’s was once considered a rare and bizarre syndrome, most often associated with the exclamation of obscene words or socially inappropriate and derogatory remarks (coprolalia), but this symptom is present in only a small minority of people with Tourette’s.

Tourette’s is no longer considered a rare condition, but it is not always correctly identified because most cases are mild and the severity of tics decreases for most children as they pass through adolescence. Between 0.4% and 3.8% of children ages 5 to 18 may have Tourette’s; the prevalence of other tic disorders in school-age children is higher, with the more common tics of eye blinking, coughing, throat clearing, sniffing, and facial movements. Extreme Tourette’s in adulthood is a rarity, and Tourette’s does not adversely affect intelligence or life expectancy.

Genetic and environmental factors play a role in the etiology of Tourette’s, but the exact causes are unknown. In most cases, medication is unnecessary. There is no effective treatment for every case of tics, but certain medications and therapies can help when their use is warranted. Education is an important part of any treatment plan, and explanation and reassurance alone are often sufficient treatment.

Comorbid conditions (co-occurring diagnoses other than Tourette’s) such as attention-deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD) are present in many patients seen in tertiary specialty clinics. These other conditions often cause more functional impairment to the individual than the tics that are the hallmark of Tourette’s; hence, it is important to correctly identify comorbid conditions and treat them.

The eponym was bestowed by Jean-Martin Charcot (1825–1893) on behalf of his resident, Georges Albert Édouard Brutus Gilles de la Tourette (1857–1904), a French physician and neurologist, who published an account of nine patients with Tourette’s in 1885.

Treatment

Case series

Patients with Tourette syndrome diagnosed according to DSM-IV TR criteria with severe medication-recalcitrant disease referred to the Hazrat Rasool Hospital, Iran University of Medical Sciences, TehranIran, were recruited for this study. They underwent bilateral anteromedial globus pallidus internus (amGPi) DBS with Medtronic Brain Neurostimulation Lead 3389. Patients were assessed using Yale Global Tic Severity Scale(YGTSS) and Gilles de la Tourette syndrome-quality of life scale (GTS-QOL) before and one year after DBS.

Six patients (four man and two women) with severe medication-recalcitrant TS, mean age of 26.33 ± 7.25 years fulfilled the follow up visits. All patients revealed significant improvement in tics severity one year after surgery. Based on YGTSS, total tic severity score decreased from 75.66 ± 16.54 to 28.33 ± 13.95, P-value:0.005. Quality of life improved significantly after DBS (26.66 ± 20.65 before and 70.00 ± 17.88 one year after surgery, P-value:0.02).

Results of this study in accordance to previous ones suggest AM-GPi DBS as an effective and well-tolerated therapeutic modality for patients with medication refractory TS 1).

2017

Giorni et al. used intra-operative microelectrode recording during stereotactic neurosurgery to guide implantation of DBS lead.

Units in the medial anterior part of GPi of 7 Tourette’s syndrome patients under general anesthesia were firing at mean and median rate of 32.1 and 21 Hz respectively (n = 101), with 45% of spikes fired during bursts and 21.3 bursts per minute. In the latero-posterior part of GPi of 7 dystonic patients under local anesthesia the mean and median activity were 46.1 and 30.6 Hz respectively (n = 27), and a mean of 21.7 bursts per minute was observed, with 30% of all spikes occurring during these bursts.

Units activity pattern – slow-regular, fast-irregular or fast-regular were present in different proportions between the two targets.

The electrophysiological characteristics of the medial-anterior part of GPi and its latero-posterior portion can be used to assist DBS electrode targeting and also support the refinement of pathophysiological models of Tourette’s syndrome and Dystonia 2).


A study of 15 patients with long-term amGPi DBS for severe TS investigated whether a specific anatomical site within the amGPi correlated with optimal clinical outcome for the measures of tics, obsessive compulsive behaviour (OCB), and mood.

Validated clinical assessments were used to measure tics, OCB, quality of life, anxiety, and depression before DBS and at the latest follow-up (17-82 months). Electric field simulations were created for each patient using information on electrode location and individual stimulation parameters. A subsequent regression analysis correlated these patient-specific simulations to percentage changes in outcome measures in order to identify any significant voxels related to clinical improvement.

A region within the ventral limbic GPi, specifically on the medial medullary lamina in the pallidum at the level of the AC-PC, was significantly associated with improved tics but not mood or OCB outcome.

This study adds further support to the application of DBS in a tic-related network, though factors such as patient sample size and clinical heterogeneity remain as limitations and replication is required 3).

Case reports

2018

Richieri et al., report the first case of a patient with severe, intractable Tourette Syndrome (TS) with comorbid Obsessive Compulsive disorder(OCD), who recovered from both disorders with gamma knife stereotactic radiosurgery following deep brain stimulation (DBS). This case highlights the possible role of the internal capsule within the neural circuitries underlying both TS and OCD, and suggests that in cases of treatment-refractory TS and comorbid OCD, bilateral anterior capsulotomy using stereotactic radiosurgery may be a viable treatment option 4).

1)

Azimi A, Parvaresh M, Shahidi G, Habibi A, Rohani S, Safdarian M, Fattahi A, Taheri M, Rohani M. Anteromedial GPi deep brain stimulation in Tourette syndrome: The first case series from Iran. Clin Neurol Neurosurg. 2018 Jul 4;172:116-119. doi: 10.1016/j.clineuro.2018.06.045. [Epub ahead of print] PubMed PMID: 29990958.

2)

Giorni A, Windels F, Stratton PG, Cook R, Silberstein P, Coyne T, Silburn PA, Sah P. Single-unit activity of the anterior Globus pallidus internus in Tourette patients and posterior Globus pallidus internus in dystonic patients. Clin Neurophysiol. 2017 Oct 16;128(12):2510-2518. doi: 10.1016/j.clinph.2017.10.003. [Epub ahead of print] PubMed PMID: 29101846.

3)

Akbarian-Tefaghi L, Akram H, Johansson J, Zrinzo L, Kefalopoulou Z, Limousin P, Joyce E, Hariz M, Wårdell K, Foltynie T. Refining the Deep Brain Stimulation Target within the Limbic Globus Pallidus Internus for Tourette Syndrome. Stereotact Funct Neurosurg. 2017 Aug 5;95(4):251-258. doi: 10.1159/000478273. [Epub ahead of print] PubMed PMID: 28787721.

4)

Richieri R, Blackman G, Musil R, Spatola G, Cavanna AE, Lançon C, Régis J. Positive clinical effects of gamma knife capsulotomy in a patient with deep brain stimulation-refractory Tourette Syndrome and Obsessive Compulsive Disorder. Clin Neurol Neurosurg. 2018 Apr 26;170:34-37. doi: 10.1016/j.clineuro.2018.04.018. [Epub ahead of print] PubMed PMID: 29723733.

Update: Tethered Cord Syndrome in Adulthood

Tethered Cord Syndrome in Adulthood

Symptoms related to a congenital tethered cord occur most commonly in childhood, so it was initially regarded as a pediatric problem; but in many patients, the diagnosis is not established until symptoms manifest in adulthood.
The number of adults in whom congenital TCS is diagnosed continues to grow as a result of better imaging and recognition of this syndrome. Pediatric TCS has been well studied in the literature, but much of the information regarding the adult population is still being defined. Patients who never undergo treatment for TCS likely have an elevated risk of developing symptoms with advancing age 1).

Epidemiology

Adult tethered cord syndrome is a rare neurological disorder that classically presents with back or leg pain, weakness, and urinary dysfunction. Spinal cord tethering has been associated with acquired Chiari malformations.

Evaluation

Radiographically: low conus medullaris (below L2) and thickened filum terminale. NB:apparent filum terminale diameter on CT myelogram may vary with concentration of contrast material.
Preoperative cystometrogram is strongly recommended, especially if the patient seems continent (postoperative changes in bladder function are not uncommon, possibly due to stretching of the lower fibers of the cauda equina).

Differential diagnosis

It is difficult to differentiate a tethered cord from a congenitally low lying conus (filum diameter is generally normal in the latter).

Treatment

Standard treatment for TCS diagnosed in adulthood remains controversial. Surgical intervention is usually indicated based on an expected natural history of disease progression in the absence of treatment.
Some adults with TCS decline surgery despite severe neurologic deficit 2).

Surgical treatment

If the only abnormality is a thickened, shortened filum terminale, then a limited lumbosacral laminectomy may suffice, with division of the filum once identified.
If a lipoma is found, it may be removed with the filum if it separates easily from neural tissues.
The filum is differentiated from nerve roots by presence of characteritics squiggly vessel on surface of filum. Also, under the microscope, the filum has a distinctively whiter appearance than the nerve roots, and ligamentous-like strands can be seen running through it. NB: intra-op electrical stimulation and recording of anal sphincter EMG are more definitive.

Technique

In the series of Gao et al. all patients received general anesthesia and took their prone position, neural electrophysiological monitoring electrode were then placed, followed by the acquisition and collection of muscle electromyography signals from the anal sphincter, bilateral musculus vastus lateralis, gastrocnemius and mesothenar. A total of 72 cases applied positive straight incision, 10 cases of lumbosacral lipoma with longitudinal incision. After exposing the dura mater spinalis, it was cut from the normal anatomical structure to the lesion. Cauda equina was managed by sharp releasing adhesion under the nerve electrophysiological monitoring, tumors were removed with the use of medical ultrasonic dissector. After the tumor was removed, the dura mater spinalis with low tonus was closed by water, and the dura mater spinalis with high tonus was formed by the autogenous fascia. For patients combined with subcutaneous giant lipoma in the lumbosacral region, the subcutaneous tumor was removed, and the drainage tube was placed into the left empty cavity, followed by pressurized dressing and vacuum aspiration 3).

Outcome

Surgical release is usually good for pain relief. However, it is poor for return of bladder function.
Results of clinical studies of surgical intervention in adulthood are encouraging 4)5) 6).
It is safe and effective for improving pain and neurological status in the majority of patients; however, patients who have undergone previous intradural detethering procedures in general fare less well, and considerable judgment is required in their management 7).
In a multivariate regression model, laminectomy, bladder dysfunction when associated to muscular weakness, and long-term (>6 months) symptoms were selected as the independent risk factors associated with poor or minimally improved (almost unchanged) surgical outcomes. When the urodynamic test showed overactive detrusor muscle, no improvement was recorded in postoperative urodynamic test. Laminoplasty (or hemilaminectomy), short-term (<6 months) symptoms, patients without lipomas, and presentation with moderate or mild symptoms seem to be proper predictors for good surgical outcomes. Further prospective studies are necessary to investigate these findings systematically. Urodynamic study can be used as a predictive tool for close follow-up of asymptomatic adult patients involved with TCS 8).

Case reports

A 68-year-old man with a history of distant T12-level spinal cord injury who presented with two weeks of progressive bilateral lower extremity weakness. The patient underwent a T12-L1 laminectomy in 1977, complicated by arachnoiditis and syringomyelia, with eventual placement of a syringo-pleural shunt. He remained neurologically stable until 2012, when he underwent a suboccipital craniectomy for Chiari decompression for new-onset headache and dysphagia. Ten days later, the patient noted progressive leg weakness and radiographic evidence of spinal cord tethering at the T11-T12 level. A T10-L1 laminectomy and medical facetectomy was undertaken for detethering with postoperative recovery of ambulatory function with assistance.
The patient presented with an unusual acquisition of tethered cord syndrome. The tethering of the spinal cord may have been triggered by arachnoid adhesions from initial lumbar surgery 35 years prior to presentation and subsequently exacerbated by alterations of CSF dynamics following Chiari decompression. Given the potentially devastating sequelae of tethered cord syndrome, investigation of CSF flow dynamics may be beneficial prior to operative intervention in patients with risk factors for a tethered cord who present with adult-onset Chiari malformation 9).
1) , 4)

Rajpal S, Tubbs RS, George T, Oakes WJ, Fuchs HE, Hadley MN, Iskandar BJ. Tethered cord due to spina bifida occulta presenting in adulthood: a tricenter review of 61 patients. J Neurosurg Spine. 2007 Mar;6(3):210-5. PubMed PMID: 17355019.
2)

Düz B, Gocmen S, Secer HI, Basal S, Gönül E. Tethered cord syndrome in adulthood. J Spinal Cord Med. 2008;31(3):272-8. PubMed PMID: 18795476; PubMed Central PMCID: PMC2565560.
3)

Gao J, Kong X, Li Z, Wang T, Li Y. Surgical treatments on adult tethered cord syndrome: A retrospective study. Medicine (Baltimore). 2016 Nov;95(46):e5454. PubMed PMID: 27861396; PubMed Central PMCID: PMC5120953.
5) , 7)

Lee GY, Paradiso G, Tator CH, Gentili F, Massicotte EM, Fehlings MG. Surgical management of tethered cord syndrome in adults: indications, techniques, and long-term outcomes in 60 patients. J Neurosurg Spine. 2006 Feb;4(2):123-31. PubMed PMID: 16506479.
6)

van Leeuwen R, Notermans NC, Vandertop WP. Surgery in adults with tethered cord syndrome: outcome study with independent clinical review. J Neurosurg. 2001 Apr;94(2 Suppl):205-9. PubMed PMID: 11302621.
8)

Abdallah A, Emel E, Abdallah BG, Asiltürk M, Sofuoğlu ÖE. Factors affecting the surgical outcomes of tethered cord syndrome in adults: a retrospective study. Neurosurg Rev. 2018 Jan;41(1):229-239. doi: 10.1007/s10143-017-0842-z. Epub 2017 Mar 14. PubMed PMID: 28293750.
9)

Jackson C, Yang BW, Bi WL, Chiocca EA, Groff MW. Adult tethered cord syndrome following Chiari decompression. World Neurosurg. 2018 Jan 31. pii: S1878-8750(18)30208-0. doi: 10.1016/j.wneu.2018.01.165. [Epub ahead of print] PubMed PMID: 29409774.

Update: White cord syndrome

White cord syndrome

Presence of intramedullary MRI hyperintensity signal on T2 weighted image in a patient with unexplained neurological deficits following a spinal cord decompression.

Epidemiology

“White cord syndrome” is a very rare condition.

Etiology

It is thought to be the result of acute reperfusion of chronically areas of spinal cord ischemia.

Diagnosis

Its hallmark is the presence of intramedullary MRI hyperintensity signal on T2 weighted image in a patient with unexplained neurologic deficits following a spinal cord decompression.

Treatment

In previous reports patients have improved following steroid therapy and acute rehabilitation 1).

Case reports

2018

Antwi et al. report an additional case of this complication in a 68-year-old man who developed acute left-sided hemiparesis after posterior cervical fusion for cervical spondylotic myelopathy. The patient improved with high dose steroid therapy 2).

2017

A 64-years old male patient with severe neck pain irradiated to both arms, gait disorder and urinary incontinence. He showed spastic tetraparesis, grip weakness and positive bilateral Hoffman sign, with a Nurick scale score of 3 and a Japanese Orthopaedic Association scale (JOA) of 13, Grade I. MRI imaging documented multiple cervical stenosis with voluminous C3–C4 and C5–C6 disc herniations associated to T2-hyperintense myelomalacic area at C3–C4 level.
Patient underwent double-level ACDF with microsurgical discectomy according to Smith Robinson technique and following anterior arthrodesis, first in C5–C6 with the placement of a titanium cage with intrabody screws (Zero P®, Depuy Synthes – Johnson & Johnson – US), then in C3–C4 level with a stand-alone titanium cage (Cervios®, Depuy Synthes – Johnson & Johnson – US). A diamond drill was used to remove osteophythes in both interbody spaces so to increase spinal cord decompression. An autologous fibrin glue was used to ameliorate haemostasis and fusion.
No surgical, nor anaesthesiological complications were observed, all neural structures were respected and intra-operative x-ray showed the correct placement of both cages. During the closure time of the superficial planes, somatosensory and motor evoked potentials suddenly decreased in voltage. When awakened, the patient showed a severe tetraparesis with complete paraplegia and severe motor weakness to upper limbs with diffuse spastic hypertonia.
A neck collar was then placed and an immediate cervical-spine CT imaging confirmed the correct execution of ACDF.
A following cervical MRI showed an enlarged T2-hyperintense area in C5–C6 level
This ischemic-edematous lesion was supposed to be a case of “white cord syndrome” imputable to a mechanism of improper cord reperfusion. A two-days NASCIS III protocol was then performed.
Three days after, a partial recovery in prehensile strength on the right hand (3/5 Medical Research Council Scale, MRC), a partial recovery in flexion of right arm (2/5 MRC), and in flexion of both legs on thighs (2/5 MRC) were observed.
Seven days after the procedure the patient was transferred to a high specialized Rehabilitation Unit with a Nurick score of 4 and a JOA of 6 3).

2013

Chin et al. report a case of complete loss of somatosensory evoked potentials (SSEPs) during elective ACDF at C4-5 and C5-6 followed by postoperative C6 incomplete tetraplegia without any discernible technical cause. A postoperative MRI demonstrated a large area of high signal changes on T2-weighted MRI intrinsic to the cord “white cord syndrome” but no residual compression. This was considered consistent with spinal cord gliosis with possible acute edema. The acute decompression of the herniated disc resulted in cord expansion and rush-in reperfusion. We postulate that this may have led to disruption in the blood brain barrier (BBB) and triggered a cascade of reperfusion injuries resulting in acute neurologic dysfunction. At 16 months postoperatively our patient is recovering slowly and is now a Nurick Grade 4 4).

References

1) , 2)

Antwi P, Grant R, Kuzmik G, Abbed K. “White Cord Syndrome” of Acute Hemiparesis after Posterior Cervical Decompression and Fusion for Chronic Cervical Stenosis. World Neurosurg. 2018 Feb 13. pii: S1878-8750(18)30296-1. doi: 10.1016/j.wneu.2018.02.026. [Epub ahead of print] PubMed PMID: 29452319.
4)

Chin KR, Seale J, Cumming V. “White cord syndrome” of acute tetraplegia after anterior cervical decompression and fusion for chronic spinal cord compression: a case report. Case Rep Orthop. 2013;2013:697918. doi: 10.1155/2013/697918. Epub 2013 Mar 4. PubMed PMID: 23533882; PubMed Central PMCID: PMC3603640.

Central Pain Syndrome

Central Pain Syndrome


List Price: $209.00

This book sheds new light on central pain, a field that is largely obscured by lack of knowledge among pain professionals at all levels, including high-end pain centers. As a matter of fact, central pain, classified as a form of neuropathic pain, remains too often a scourge for those affected due to the ignorance of pain therapists worldwide and enduring misconceptions at the academic level. By weighing up the relevant evidence, the authors aim to remedy the situation by providing clear-cut, no-nonsense, unbiased and directly applicable clinical information.
The clinically sound guidelines presented here are based on the authors’ twenty years of treating patients and conducting research in the field. The book will be an invaluable guide for neurologists, neurosurgeons, anesthesiologists, pain therapists as well as physiotherapists.

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