syndrome

Tourette’s syndrome

Tourette’s syndrome

A disorder characterized by random, repeated, and stereotyped motor tic or vocal tics for over > 1 year, 1) usually in several “bouts” per day. Onset is before age 18 years (mean age: 5 years). Male: female ratio is 4:1. The tics may be socially inappropriate, as such, are disabling. TS is often associated with OCD, ADHD & other personality disorders.

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.

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.

Associations

Cavum septum pellucidum may also indicate disruption of neurodevelopment and has been associated with neurodevelopmental and psychiatric conditions including bipolar disorder, Tourette’s syndrome, obsessive-compulsive disorder, and schizophrenia, among others 2)

Clinical features

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.

Characterized by motor and vocal tics, which is often associated with psychiatric comorbidities. Dysfunction of basal ganglia pathways might account for the wide spectrum of symptoms in TS patients. Although psychiatric symptoms may be related to limbic networks, the specific contribution of different limbic structures remains unclear.

Temiz et al. used tractography to investigate cortical connectivity with the striatal area (caudate, putamen, core and shell of the nucleus accumbens), the subthalamic nucleus (STN), and the adjacent medial subthalamic region (MSR) in 58 TS patients and 35 healthy volunteers. 82% of TS patients showed psychiatric comorbidities, with significantly higher levels of anxiety and impulsivity compared to controls. Tractography analysis revealed significantly increased limbic cortical connectivity of the left MSR with the entorhinal cortex (BA34), insular cortex (BA48), and temporal cortex (BA38) in TS patients compared to controls. Furthermore, they found that left insular-STN connectivity was positively correlated with impulsivity scores for all subjects and with anxiety scores for all subjects, particularly for TS. The study highlights a heterogenous modification of limbic structure connectivity in TS, with specific abnormalities found for the subthalamic area. Abnormal connectivity with the insular cortex might underpin the higher level of impulsivity and anxiety observed in Tourette syndrome 3).

Treatment

see Tourette’s syndrome treatment.

Case series

Tourette’s syndrome case series.

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)

Kurlan R. Clinical practice. Tourette’s Syndrome. N Engl J Med. 2010; 363:2332–2338
2)

Silk T, Beare R, Crossley L, et al. Cavum septum pellucidum in pediatric traumatic brain injury. Psychiatry Res. 2013; 213:186–192
3)

Temiz G, Atkinson-Clement C, Lau B, Czernecki V, Bardinet E, Francois C, Worbe Y, Karachi C. Structural hyperconnectivity of the subthalamic area with limbic cortices underpins anxiety and impulsivity in Tourette syndrome. Cereb Cortex. 2022 Oct 30:bhac408. doi: 10.1093/cercor/bhac408. Epub ahead of print. PMID: 36310093.
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.

Anterior sacral meningocele in Marfan syndrome

Anterior sacral meningocele in Marfan syndrome

Twenty-four Marfan and 2 Loeys-Dietz patients had anterior sacral meningocele at follow-up, compared with 21 and 1, respectively, at baseline. Three Marfan patients developed herniation of a nerve root sleeve during follow-up. This was not seen in other individuals. The dural sac ended significantly lower at follow-up, and the dural sac ratio at level L5 was significantly increased from baseline in the Marfan patients.

In Marfan and Loeys-Dietz syndrome, dural ectasia may present or worsen during adulthood. The cut-off value of dural sac ratio at level S1 is suggested elevated to 0.64. The results from the present study may help as guidance for appropriate follow-up of patients with dural ectasia 1).

Case reports

A case of a 46-year-old woman who presented with urinary incontinence, early satiety, and back pain in the setting of a known anterior sacral meningocele. Before operative management, the anterior sacral meningocele ruptured with the patient presenting signs and symptoms of intracranial hypotension. Conservative management did not alleviate the pain. She was ultimately managed with posterior sacroplasty followed by anterior sacral meningocele resection and placement of a lumboperitoneal shunt. The patient did not have reaccumulation of the meningocele or recurrent symptoms at the latest follow-up.

The progression of dural ectasia in Marfan syndrome to an anterior sacral meningocele is uncommon. It is important to identify the characteristics associated with an expanding dural ectasia as this patient’s symptoms progressed over time and the meningocele grew large. Given its rarity, there are no guidelines in place regarding size at which repair of an anterior sacral meningocele should occur prophylactically. It is important to review these cases in order continue to learn about progression, management, and outcomes of patients with an anterior sacral meningocele. 2).

A 43-year-old woman with a history of Marfan syndrome and a large ASM was referred for neurosurgical intervention. The ASM was filling the pelvic cavity and causing severe compression of the bladder. The patient underwent surgical decompression of the cyst through an anterior transabdominal approach and closure of the fistulous tract with a pedicled omental flap. This is the first reported case of successful closure of an ASM with an omental flap. At the 6-month follow-up, the ASM had not recurred on imaging and the patient’s symptoms had resolved. Anterior sacral meningoceles are rare lesions that often require neurosurgical intervention. Although most can be treated posteriorly, large ASMs compressing the abdominal or pelvic organs may require a transabdominal approach. Moreover, ASMs with wide dural stalks may benefit from closure with an omental flap. 3).

A 43-year-old man diagnosed with Marfan syndrome suffered sacrococcygeal trauma. He was admitted to the emergency room due to symptoms of headache, nausea, and lower limb subjective weakness. CT and MRI showed a large retroperitoneal mass with hemorrhagic content close to the sacrum. Likewise, the MRI showed an image compatible with subarachnoid hemorrhage in the thoracic spinal area, cerebral convexity, and the basal cisterns. The patient went into surgery for an anterior abdominal approach in the midline to reduce the content of the lesion, and subsequently, in the same act, a posterior approach was done with an S1-S2 laminectomy and obliteration of the pedicle. Postoperative MRI 5 months later showed resolution of the ASM.

Anterior sacral meningocele is characterized by herniation of the dura mater and the arachnoid mater outside the spinal canal through a defect of the sacrum. We add the risk of bleeding after trauma-never seen in the literature-as one of the possible inherent complications of this lesion.

This report highlights a complication never seen in the literature of a relatively rare condition. In our case, the combined approach was effective for both clinical control and lesion regression. 4).

A patient with Marfan’s syndrome and ASMs who was referred to gynaecology owing to dysmenorrhoea and left-sided pelvic pain radiating to the left leg. A transvaginal ultrasound scan (TVUS) detected a left pelvic cystic tubular structure, attributed to a hydrosalpinx, which, in retrospect, likely corresponded to the ASM. The patient went on to have TVUS-guided drainage of this cystic structure, resulting in an ASM abscess. It is difficult to distinguish ASM from the vastly more common hydrosalpinx using TVUS alone, and in patients with an atypical appearing posteriorly positioned cystic pelvic lesion or in the presence of underlying conditions known to be associated with ASMs, MRI should be considered before any interventional procedure to drain the suspected hydrosalpinx transvaginally. The patient was successfully treated using a minimally invasive CT-guided posterior trans-sacral drainage technique. 5).

A 20-year old female with Marfan syndrome who presented with abdominal distention that was misdiagnosed as an ovarian cyst on pelvic ultrasound. Pelvic magnetic resonance (MR) imaging showed large, well-defined multiloculated intrasacral and presacral cysts communicating via two separate broad necks and extending through defects in anterior aspect of sacral vertebrae. This case emphasizes that anterior sacral meningocele should be considered in the differential diagnosis of cases with pelvic cysts particularly in patients with underlying connective tissue disorders. Because severe neurologic complications or even death may occur without proper preoperative planning in such cases, MR imaging should always be performed for evaluation and characterization of pelvis cystic lesions. 6).

A young woman with Marfan syndrome who was being treated with anticoagulants for a prosthetic heart valve and who presented with a spontaneous retroperitoneal hemorrhage requiring surgical evacuation. No CSF leak was encountered at surgery, but she developed progressively more severe positional headaches over the following year. She then experienced the sudden onset of acute urinary obstruction, at which time CT revealed a 17 × 15 × 13-cm presacral pseudomeningocele communicating with the thecal sac through a sacral bone defect. An anterior surgical approach was used for drainage of the pseudomeningocele as well as for primary closure of the dural defect with a bovine pericardial patch and autologous subcutaneous fat graft. After a short period of lumbar subarachnoid drainage of the CSF, the patient was able to resume normal activity without recurrent symptoms. To the authors’ knowledge, such a pseudomeningocele in a patient with Marfan syndrome has been reported only twice, and this case features the largest pseudomeningocele to date. They also review the pertinent literature regarding presentation, diagnosis, and management of these lesions. 7).

Relapse of Escherichia coli meningitidis due to sacral meningocele in Marfan syndrome, treated only with antibiotherapy 8).

Surgical Treatment of Anterior Sacral Meningoceles in Patients with Marfan Syndrome: A Report of Three Cases 9).

A case of bacterial meningitis secondary to fistulous communication between a sacral meningocele and sigmoid colon in the setting of diverticulitis 10).

Five women who underwent laparoscopic transperitoneal surgery were clinically, radiologically, and surgically evaluated.

Result: All 5 patients underwent laparoscopic transperitoneal surgery and showed satisfactory results. They had no major complications. Three patients had headaches as minor complications, but it was gone in at most 3 days. Decrease in operative time, blood loss, and length of hospitalization were the advantages of the procedure.

The laparoscopic approach to treating anterior sacral meningocele was feasible and safe, with only minor complications. 11).

A woman with Marfan’s syndrome presenting with a clinical picture of acute gastroenteritis in whom severe bilateral hydroureteronephrosis associated to a neurogenic bladder and a giant anterior sacral meningocele was diagnosed incidentally. The importance of this case lies in the fact that the patient was asymptomatic despite the significant visceral repercussions already occurring that led to questioning of whether MRI follow-up would still be advisable even in the absence of symptoms. 12).

A 46-year-old woman with Marfan’s syndrome exhibiting an incomplete Currarino triad and recurrent bacterial meningitis which recurred three times in about six months. An anterior sacral meningocele (ASM) was noted in a lumbar MRI, and multiple bone defects in the sacrum were noted in 3D-CT. Surgical approach to prevent the recurrence of infection was limited to plasty for the meningocele, but no meningitis has been observed for two years. Radical surgery should be considered in cases with ASM who recurred bacterial meningitis. 13).

A 52 year old woman with Marfan syndrome who presented with a significantly large anterior sacral meningocele without having associated symptoms. In light of this case, we recommend that asymptomatic Marfan patients with dural ectasia should be closely observed without need for immediate surgical intervention 14).

18-year-old man with Marfan syndrome, diagnosed upon MRI morphological evaluation which showed a huge cystic mass in the pelvic space. Surgical excision even if curative was not performed in consideration of a stationary picture after one year since diagnosis. 15).

Two cases presenting as nongynaecological pelvic masses are described highlighting the clinical difficulty in diagnosis and the classical radiological findings 16).

Anterior sacral meningocele presenting as a pelvic/abdominal mass in a patient with Marfan syndrome 17).

The first case of a giant anterior sacral meeningocele rapidly cured by a simple endoscopic procedure 18). The postoperative course of the patient was characterized by immediate disappearance of the preoperative clinical signs. Computed tomographic scans demonstrated progressive complete collapse of the anterior sacral meningocele and partial resolution of the intrasacral component 19).

A marfanoid patient underwent celiotomy for a pelvic mass and was found to have an anterior sacral meningocele. Nine years prior to that time she had undergone surgery because of a “sacrococcygeal cyst,” which in retrospect seemed to be a posterior meningocele 20).

Purulent meningitis from surgical inoculation of an anterior sacral meningocele 21).

Anterior sacral meningocele in association with Marfan’s syndrome 22).

1)

Böker T, Vanem TT, Pripp AH, Rand-Hendriksen S, Paus B, Smith HJ, Lundby R. Dural ectasia in Marfan syndrome and other hereditary connective tissue disorders: a 10-year follow-up study. Spine J. 2019 Aug;19(8):1412-1421. doi: 10.1016/j.spinee.2019.04.010. Epub 2019 Apr 15. PMID: 30998996.
2)

Hollenberg AM, Baldwin AL, Mesfin A, Silberstein H. Rupture of Giant Anterior Sacral Meningocele in a Patient with Marfan Syndrome: Diagnosis and Management. World Neurosurg. 2018 Nov;119:137-141. doi: 10.1016/j.wneu.2018.07.249. Epub 2018 Aug 6. PMID: 30092475.
3)

Paisan GM, Crandall KM, Chen S, Burks SS, Sands LR, Levi AD. Closure of a giant anterior sacral meningocele with an omental flap in a patient with Marfan syndrome: case report. J Neurosurg Spine. 2018 Aug;29(2):182-186. doi: 10.3171/2018.1.SPINE171303. Epub 2018 May 25. PMID: 29799321.
4)

Gilete-Tejero IJ, Ortega-Martínez M, Mata-Gómez J, Rico-Cotelo M, Bernal- García LM, Yerga-Lorenzana B, Casado-Naranjo I. Anterior sacral meningocele presenting as intracystic bleeding. Eur Spine J. 2018 Jul;27(Suppl 3):276-280. doi: 10.1007/s00586-017-5128-1. Epub 2017 May 18. PMID: 28523383.
5)

Jawad S, Ejindu V, Johnson D, Shah MA, Abbasi MA, Ojha K, Papadakos N. Transvaginal ultrasound-guided aspiration of an anterior sacral meningocele masquerading as a hydrosalpinx, resulting in abscess formation. BJR Case Rep. 2016 Sep 3;3(1):20160037. doi: 10.1259/bjrcr.20160037. PMID: 30363340; PMCID: PMC6159307.
6)

Sahin N, Genc M, Kasap E, Solak A, Korkut B, Yilmaz E. Anterior Sacral Meningocele Masquerading as an Ovarian Cyst: A Rare Clinical Presentation Associated with Marfan Syndrome. Clin Pract. 2015 Apr 24;5(2):752. doi: 10.4081/cp.2015.752. PMID: 26236457; PMCID: PMC4500879.
7)

Stone JG, Bergmann LL, Takamori R, Donovan DJ. Giant pseudomeningocele causing urinary obstruction in a patient with Marfan syndrome. J Neurosurg Spine. 2015 Jul;23(1):77-80. doi: 10.3171/2014.11.SPINE131086. Epub 2015 Apr 24. PMID: 25909269.
8)

Bigaré M, Lesaffre X, Delassus JL, Bakir R, Bouldouyre MA. Rechute de méningite à Escherichia coli due à un méningocèle sacré dans le cadre d’une maladie de Marfan, traitée par antibiothérapie prolongée seule [Relapse of Escherichia coli meningitidis due to sacral meningocele in Marfan syndrome, treated only with antibiotherapy]. Presse Med. 2014 Jan;43(1):93-5. French. doi: 10.1016/j.lpm.2013.02.330. Epub 2013 Jul 19. PMID: 23876649.
9)

Ebnet J, Krauss JK, Lorenz M, Bektas H, Nakamura M. Surgical Treatment of Anterior Sacral Meningoceles in Patients with Marfan Syndrome: A Report of Three Cases. JBJS Case Connect. 2012 Apr-Jun;2(2):e16. doi: 10.2106/JBJS.CC.K.00040. PMID: 29252417.
10)

Samet JD, Johnson PT, Horton KM, Fishman EK. Diverticulitis complicated by fistulous communication of sigmoid colon with anterior sacral meningocele in a patient with Marfan syndrome. Radiol Case Rep. 2015 Dec 7;7(1):442. doi: 10.2484/rcr.v7i1.442. PMID: 27326266; PMCID: PMC4899866.
11)

Trapp C, Farage L, Clatterbuck RE, Romero FR, Rais-Bahrami S, Long DM, Kavoussi LR. Laparoscopic treatment of anterior sacral meningocele. Surg Neurol. 2007 Oct;68(4):443-8; discussion 448. doi: 10.1016/j.surneu.2006.11.067. PMID: 17905071.
12)

Santana JM, Gómez A, Alemán P, Travieso MM. Ureterohidronefrosis severa asociada a meningocele sacro anterior gigante asintomático: presentación de un caso y revisión de la literatura [Severe hydroureteronephrosis associated to asymptomatic giant anterior sacral meningocele: a case report and review of the literature]. Radiologia. 2007 Jan-Feb;49(1):43-6. Spanish. doi: 10.1016/s0033-8338(07)73715-3. PMID: 17397621.
13)

Hatano A, Akiyama K, Nagayama M, Takagi S. [Case of Marfan’s syndrome with anterior sacral meningocele along with recurring bacterial meningitis]. Rinsho Shinkeigaku. 2006 Sep;46(9):658-60. Japanese. PMID: 17260811.
14)

Nallamshetty L, Ahn NU, Ahn UM, Nallamshetty HS, Rose PS, Buchowski JM, Sponseller PD. Dural ectasia and back pain: review of the literature and case report. J Spinal Disord Tech. 2002 Aug;15(4):326-9. doi: 10.1097/00024720-200208000-00012. PMID: 12177551.
15)

Rigante D, Segni G. Anterior sacral meningocele in a patient with Marfan syndrome. Clin Neuropathol. 2001 Mar-Apr;20(2):70-2. PMID: 11327300.
16)

Voyvodic F, Scroop R, Sanders RR. Anterior sacral meningocele as a pelvic complication of Marfan syndrome. Aust N Z J Obstet Gynaecol. 1999 May;39(2):262-5. doi: 10.1111/j.1479-828x.1999.tb03390.x. PMID: 10755797.
17)

Schneider MB, Dittmar S, Boxer RA. Anterior sacral meningocele presenting as a pelvic/abdominal mass in a patient with Marfan syndrome. J Adolesc Health. 1993 Jun;14(4):325-8. doi: 10.1016/1054-139x(93)90182-o. PMID: 8347646.
18)

Raftopoulos C, Delecluse F, Braude P, Rodesh C, Brotchi J. Anterior sacral meningocele and Marfan syndrome: a review. Acta Chir Belg. 1993 Jan- Feb;93(1):1-7. PMID: 8470436.
19)

Raftopoulos C, Pierard GE, Rétif C, Braude P, Brotchi J. Endoscopic cure of a giant sacral meningocele associated with Marfan’s syndrome: case report. Neurosurgery. 1992 May;30(5):765-8. doi: 10.1097/00006123-199205000-00020. PMID: 1584392.
20)

Barter JF, Addison WA, Rosenberg ER, Hammond CB. Anterior sacral meningocele presenting as a pelvic mass and diagnosed only at celiotomy after an extensive workup. A case report. J Reprod Med. 1983 Oct;28(10):684-6. PMID: 6655630.
21)

le Mercier Y, Decazes JM, Mechali D, Redondo A, Aboulker J, Coulaud JP. Méningite purulente par inoculation chirurgicale d’une méningocèle sacrée antérieure. Une complication rare de la maladie de Marfan [Purulent meningitis from surgical inoculation of an anterior sacral meningocele: a rare complication of Marfan’s disease (author’s transl)]. Ann Med Interne (Paris). 1980;131(5):289-90. French. PMID: 7004305.
22)

Strand RD, Eisenberg HM. Anterior sacral meningocele in association with Marfan’s syndrome. Radiology. 1971 Jun;99(3):653-4. doi: 10.1148/99.3.653. PMID: 5578713.

Sickle Cell Disease Associated Moyamoya Syndrome

Sickle Cell Disease Associated Moyamoya Syndrome

Moyamoya syndrome (MMS) is a relatively uncommon vascular complication of sickle cell disease (SCD) characterized by progressive stenosis of the supraclinoid carotid arteries and development of typical collaterals

Sickle Cell Disease is associated with moyamoya-like changes on cerebral angiographic imaging in 43% of patients. Cerebral aneurysms,arteriovenous malformations, and dural arteriovenous fistulas (AVFs) have been described in association with SCD and moyamoya disease.

Moyamoya syndrome increases the risk of stroke in sickle cell disease

Treatment

Collaborative management between hematology and neurosurgery offers effective strategies to reduce stroke risk in these patients.

Revascularization is associated with a significant reduction in stroke risk, both relative to prerevascularization rates and compared with medical management. According to these findings, surgical revascularization offers a safe and durable preventative therapy for stroke and should be pursued aggressively in this patient population 1).

Case series

A retrospective cohort study of medically managed vs surgically revascularized patients with moyamoya syndrome and sickle cell disease was conducted. Demographic data and outcomes including the number of prediagnosis, postdiagnosis, and postrevascularization strokes were collected. Risk factors for stroke were identified using a binary logistic regression model, and stroke rates and mortality between groups were compared.

Of the 29 identified patients, 66% were medically managed and 34% underwent surgical revascularization (50% direct and 50% indirect). Calculated stroke rates were 1 per 5.37 (medical management), 1 per 3.43 (presurgical revascularization), and 1 per 23.14 patient-years (postsurgical revascularization). There was 1 surgical complication with no associated permanent deficits. No risk factors for stroke after time of diagnosis were found to be significant.

The results of this study demonstrate that revascularization is associated with a significant reduction in stroke risk, both relative to prerevascularization rates and compared with medical management. According to these findings, surgical revascularization offers a safe and durable preventative therapy for stroke and should be pursued aggressively in this patient population 2).

Case reports

Lo Presti et al. present the case of a 15-year-old boy with Sickle cell disease SCD-associated moyamoya disease harboring a intracranial pial arteriovenous fistula pAVF who developed a de novo venous aneurysm 8 months after undergoing indirect superficial temporal artery–middle cerebral artery (MCA) bypass that was complicated by bilateral ischemia of the MCA territory. The pAVF was successfully treated with transarterial embolization using Onyx. The authors describe the possible pathophysiological mechanisms and management strategies for this rare occurrence 3).

Slingerland et al. described a challenging case where a patient with sickle cell disease undergoing standard of care management as prescribed by the Stroke Prevention Trial in Sickle Cell Anemia (STOP) and revascularization with pial synangiosis subsequently developed rapidly progressive disease in other cerebral vessels and suffered ischemic hemispheric stroke. This case demonstrates the success of management in accordance with American Heart Association (AHA) and American Stroke Association (ASA) guidelines, but also demonstrates critical areas where we lack understanding of disease progression 4).

1) , 2)

Newman S, McMahon JT, Boulter JH, Malcolm JG, Revuelta Barbero JM, Chern JJ, Barrow DL, Pradilla G. Revascularization Is Associated With a Reduced Stroke Risk in Patients With Sickle Cell-Associated Moyamoya Syndrome. Neurosurgery. 2022 Feb 10. doi: 10.1227/NEU.0000000000001847. Epub ahead of print. PMID: 35132969.
3)

Lo Presti A, Weil AG, Fallah A, Peterson EC, Niazi TN, Bhatia S. Treatment of a cerebral pial arteriovenous fistula in a patient with sickle cell disease-related moyamoya syndrome: case report. J Neurosurg Pediatr. 2015 May 22:1-5. [Epub ahead of print] PubMed PMID: 26053963.
4)

Slingerland AL, Karsten MB, Smith ER, Sobota AE, See AP. Two Sides of a Coin: Case Report of Unilateral Synangiosis and Contralateral Stroke Highlighting Consequences of Disease Progression and Efficacy of Revascularization in Sickle Cell Disease Associated Moyamoya Syndrome. Acta Haematol. 2021 Dec 8. doi: 10.1159/000521361. Epub ahead of print. PMID: 34879377.

Down syndrome

Down syndrome

Down syndrome is a multiple malformation syndrome due to the trisomy of chromosome 21.

Complications

Down syndrome may be associated with various neurologic complications such as moyamoya disease, cervical spinal cord compression due to atlanto-axial subluxation, and basal ganglia damage, as well as epileptic seizures and stroke 1).

Down syndrome is associated with ligamentous laxity of the spine. This has implications whenever a fusion is contemplated, as adjacent segment failure with kyphosis is very common. Ligamentous laxity may also result in atlanto-axial subluxation (AAS).

Atlanto-axial subluxation in Down syndrome

Atlanto-axial subluxation in Down syndrome

Neurological complications

(Cerebral) amyloid angiopathy may be more prevalent in patients with Down syndrome.

Many cases of Down syndrome accompanied by isolated neurologic manifestations have been reported in children; however, Down syndrome with multiple neurologic conditions is rare 2).

There is epidemiological evidence that individuals with Down syndrome are at decreased risk for solid tumors including brain tumors. It has been suggested that some genes expressed on the extra copy of chromosome 21 act as tumor suppressor genes and contribute to the protection against tumorigenesis.

Yolk sac tumor 3)

Yamamoto et al. report the first Down syndrome patient, an 8-year-old boy, with a meningioma in the posterior fossa. The diagnosis was based on histological study of the surgically resected tumor. Postoperatively his neurological status improved and there was no tumor regrowth in the next 2 years. Fluorescence in situ hybridization (FISH) for chromosome 22 confirmed high allele loss involving the NF2 gene locus, a finding typical in meningiomas. FISH also revealed chromosome 21 heterogeneity in tumor cells; not only cells with trisomy 21 but also cells with disomy and monosomy 21 were present. All blood cells from the patient manifested trisomy 21.

This finding suggests that deletion of the chromosome 21 allele may be associated with the tumorigenesis of meningioma in Down syndrome. It supports the hypothesis that some genes whose expression is increased on the extra copy of chromosome 21 function as tumor suppressor genes and that they contribute to the reduced tumor incidence in individuals with Down syndrome 4).

Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer disease (AD) 5).

Individuals with Down syndrome (DS) are at increased risk of developing AD in adulthood as a result of chromosome 21 trisomy and triplication of the amyloid precursor protein (APP) gene. In both conditions, the central nervous system (CNS) basal forebrain cholinergic system progressively degenerates, and such changes contribute to the manifestation of cognitive decline and dementia. Given the strong dependency of these neurons on nerve growth factor (NGF), it was hypothesized that their atrophy was caused by NGF deficits. However, in AD, the synthesis of NGF is not affected at the transcript level and there is a marked increase in its precursor, proNGF. This apparent paradox remained elusive for many years 6).

Down syndrome results in neuromotor impairment that affects selective motor control, compromising the acquisition of motor skills and functional independence.

A study received approval from the Institutional Review Board of Universidade Nove de Julho (Sao Paulo,Brazil) under process number 1.540.113 and is registered with the Brazilian Registry of Clinical Trials (N° RBR3PHPXB). The participating institutions have presented a declaration of participation. The volunteers will be permitted to drop out of the study at any time with no negative repercussions. The results will be published and will contribute evidence regarding the use of this type of intervention on children 7).

Cervical spine pathologies

Cervical spine pathologies are common in Down syndrome (DS) patients. Cervical pathologies may cause cord compression and neurologic deterioration if left untreated. Complication rates of 73-100% have been reported in DS patients after cervical spine surgery in historical studies.

Current techniques may improve pseudarthrosis (p = 0.009), LOR (p = 0.043), and first attempt (p = 0.038) and overall fusion rates (p = 0.018) compared with historical studies. Complications continue to challenge most patients (82.4%). A total of 16 of 17 patients (94.1%) demonstrated stabilization or improvement in neurologic status. Apparent successful outcome in the majority appears to warrant the high complication risk associated with cervical spine surgery in DS patients. The anterior approach resulted in a higher risk of complications than posterior (p = 0.032). Siemionow et al report a higher than expected incidence of pseudarthrosis in DS patients receiving rhBMP-2, putting its benefit in DS patients into question 8).

Mouse model of Down syndrome

see Ts65Dn.

References

1)

Hwang SW, Jea A. A review of the neurological and neurosurgical implications of Down syndrome in children. Clin Pediatr (Phila). 2013 Sep;52(9):845-56. doi: 10.1177/0009922813491311. Epub 2013 Jun 6. Review. PubMed PMID: 23743011.
2)

Lee KY, Lee KS, Weon YC. Asymptomatic moyamoya syndrome, atlantoaxial subluxation and basal ganglia calcification in a child with Down syndrome. Korean J Pediatr. 2013 Dec;56(12):540-3. doi: 10.3345/kjp.2013.56.12.540. Epub 2013 Dec 20. PubMed PMID: 24416050; PubMed Central PMCID: PMC3885790.
3)

Sugimoto K, Ideguchi M, Sadahiro H, Yoshikawa K, Goto H, Nomura S, Fujii M, Suzuki M. Yolk sac tumor of the bilateral basal ganglia in a patient with Down syndrome. Brain Tumor Pathol. 2013 Oct;30(4):247-52. doi: 10.1007/s10014-012-0134-9. Epub 2013 Jan 11. Review. PubMed PMID: 23306965.
4)

Yamamoto T, Shinojima N, Todaka T, Nishikawa S, Yano S, Kuratsu JI. Meningioma in Down syndrome – Case Report. World Neurosurg. 2015 Apr 8. pii: S1878-8750(15)00365-4. doi: 10.1016/j.wneu.2015.03.065. [Epub ahead of print] PubMed PMID: 25862935.
5)

Chang CY, Chen SM, Lu HE, Lai SM, Lai PS, Shen PW, Chen PY, Shen CI, Harn HJ, Lin SZ, Hwang SM, Su HL. N-butylidenephthalide Attenuates Alzheimer’s Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons. Sci Rep. 2015 Mar 4;5:8744. doi: 10.1038/srep08744. PubMed PMID: 25735452; PubMed Central PMCID: PMC4348654.
6)

Iulita MF, Cuello AC. Nerve growth factor metabolic dysfunction in Alzheimer’s disease and Down syndrome. Trends Pharmacol Sci. 2014 Jul;35(7):338-48. doi: 10.1016/j.tips.2014.04.010. Epub 2014 Jun 21. Review. PubMed PMID: 24962069.
7)

Lopes JBP, Grecco LAC, Moura RCF, Lazzari RD, Duarte NAC, Miziara I, Melo GEL, Dumont AJL, Galli M, Santos Oliveira C. Protocol study for a randomised, controlled, double-blind, clinical trial involving virtual reality and anodal transcranial direct current stimulation for the improvement of upper limb motor function in children with Down syndrome. BMJ Open. 2017 Aug 11;7(8):e016260. doi: 10.1136/bmjopen-2017-016260. PubMed PMID: 28801420.
8)

Siemionow K, Hansdorfer M, Janusz P, Mardjetko S. Complications in Adult Patients with Down Syndrome Undergoing Cervical Spine Surgery Using Current Instrumentation Techniques and rhBMP-2: A Long-Term Follow-Up. J Neurol Surg A Cent Eur Neurosurg. 2016 Jul 22. [Epub ahead of print] PubMed PMID: 27448197.

Deep brain stimulation for Meige syndrome

Deep brain stimulation for Meige syndrome

A well-established therapeutic option is deep brain stimulation (DBS), and the target in bilateral globus pallidus internus (GPi DBS) demonstrated satisfactory short- and long-term efficacy. However, some patients present minor or suboptimal responses after GPi DBS, and in those cases, rescue DBS may be appropriate 1).

A retrospective study to assess the efficacy and safety of bilateral GPi stimulation in 40 patients with primary Meige syndrome who responded poorly to medical treatments or botulinum toxin injections. All participants were postoperatively followed up at the outpatient clinic, and their motor functions were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The severity of patients’ dystonia was evaluated before surgery and at follow-up neurostimu-lation.

Results: The implanted stimulator was turned on 1 month after surgery. All 40 patients received monopolar stimulation using the following parameters: voltage 2.5-3.5 V (average: 2.6 ± 0.8 V), frequency 60-160 Hz (average: 88.0 ± 21.3 Hz), and pulse width 60-185 μS (average: 90.0 ± 21.1 μS). In 28 of 40 patients, the symptoms had signifi-cantly improved within 1 week of stimulation. Most of the patients had been followed up for 6-24 months (average: 15.0 ± 7.8 months). The clinical symptoms of all patients had significantly improved. At 6, 12, and 24 months after surgery, the BFMDRS subscores of eyes, mouth, speech, and swallowing were significantly lower, and subscores of mouth movement showed progressively decreased with prolonged stimulation time. The overall improvement rate was 83%. Five adverse events occurred in the 40 patients; all of these events resolved without permanent sequelae.

Bilateral GPi-DBS demonstrated satisfactory long-term efficacy in the treatment of primary Meige syndrome and could serve as an effective and safe option 2).

A study explored the predictors of clinical outcome in patients with Meige syndrome who underwent DBS.

Twenty patients who underwent DBS targeting the bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) at the Chinese People’s Liberation Army General Hospital from August 2013 to February 2018 were enrolled in the study. Their clinical outcomes were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale at baseline and at the follow-up visits; patients were accordingly divided into a good-outcome group and a poor-outcome group. Putative influential factors, such as age and course of disease, were examined separately, and the factors that reached statistical significance were subjected to logistic regression analysis to identify predictors of clinical outcomes.

Four factors showed significant differences between the good- and poor-outcome groups: 1) the DBS target (STN vs GPi); 2) whether symptoms first appeared at multiple sites or at a single site; 3) the sub-item scores of the mouth at baseline; and 4) the follow-up period (p < 0.05). Binary logistic regression analysis revealed that initial involvement of multiple sites and the mouth score were the only significant predictors of clinical outcome.

The severity of the disease in the initial stage and presurgical period was the only independent predictive factor of the clinical outcomes of DBS for the treatment of patients with Meige syndrome 3).

A total of 6 patients seen between 2002 and 2010 with craniofacial and craniocervical dystonia symptoms were identified from the University of Florida Institutional Review Board approved database. Patients were videotaped using a standardized protocol, and tapes were randomized and blindly reviewed by a movement disorders neurologist. The Unified Dystonia Rating Scale improved 31.6 ± 23.2% (range: 3.4-63.2%) at 6 months and 63.7 ± 35.3% (range: 6.3-100%) at 12 months. The Burke-Fahn-Marsden Dystonia Rating Scale improved 45.3 ± 29.5% (range: 4.7-75.0%) at 6 months and 61.8 ± 30.9% (range: 16.6-100%) at 12 months. One patient significantly had a very large improvement with little evidence of residual dystonia. Blepharospasm improved in all patients, whereas speech and swallowing did not improve in this cohort. Two patients improved with unilateral GPi-DBS, although one required a contralateral DBS later in the disease course. Two patients were managed with low-frequency stimulation (<100 Hz). Two patients had less than 20% benefit. GPi-DBS for cranio-facial and craniocervical symptoms is an effective strategy to manage a subset of patients who remain unresponsive to optimized medical management. Unilateral stimulation may be an option for some patients, but it remains unclear whether response to single-sided stimulation will be sustainable. The mixed results of this GPi-DBS case series highlight the need for a careful re-examination of selection criteria, alternative brain targets, and possibly rescue leads for patients who are non-responders to the GPi target 4).

Lyons report the long-term results of bilateral globus pallidus internus (GPi) or subthalamic nucleus (STN) stimulation in 3 patients with Meige syndrome and 1 patient with Parkinson’s disease and associated craniofacial dystonia treated at their center.

Initial 12-month and long-term follow-up Burke-Fahn-Marsden scores were substantially improved in all 4 patients compared with preoperative scores.

Bilateral GPi DBS may be an effective and safe treatment for medically refractory Meige syndrome. The results are comparable with those reported in the literature. Sustained and long-term improvement in symptoms does appear to be reproducible across reports. The authors’ patient with Parkinson’s disease and associated craniofacial dystonia syndrome undergoing bilateral STN DBS noted immediate and sustained improvement in his symptoms. Further study is required, but these results, along with the other reports, suggest that bilateral GPi DBS is an effective treatment for medically refractory Meige syndrome 5).

Sobstyl M, Ząbek M, Mossakowski Z, Zaczyński A. Pallidal deep brain stimulation in the treatment of Meige syndrome. Neurol Neurochir Pol. 2014;48(3):196-9. doi: 10.1016/j.pjnns.2014.05.008. Epub 2014 Jun 6. PubMed PMID: 24981184.

1)

Aragão VT, Barbosa Casagrande SC, Listik C, Teixeira MJ, Barbosa ER, Cury RG. Rescue Subthalamic Deep Brain Stimulation for Refractory Meige Syndrome. Stereotact Funct Neurosurg. 2021 Apr 23:1-3. doi: 10.1159/000515722. Epub ahead of print. PMID: 33895729.
2)

Tian H, Yu Y, Zhen X, Zhang L, Yuan Y, Zhang B, Wang L. Long-Term Efficacy of Deep Brain Stimulation of Bilateral Globus Pallidus Internus in Primary Meige Syndrome. Stereotact Funct Neurosurg. 2019;97(5-6):356-361. doi: 10.1159/000504861. Epub 2020 Jan 10. PMID: 31927550.
3)

Wang X, Mao Z, Cui Z, Xu X, Pan L, Liang S, Ling Z, Yu X. Predictive factors for long-term clinical outcomes of deep brain stimulation in the treatment of primary Meige syndrome. J Neurosurg. 2019 Apr 5:1-9. doi: 10.3171/2019.1.JNS182555. [Epub ahead of print] PubMed PMID: 30952124.
4)

Limotai N, Go C, Oyama G, Hwynn N, Zesiewicz T, Foote K, Bhidayasiri R, Malaty I, Zeilman P, Rodriguez R, Okun MS. Mixed results for GPi-DBS in the treatment of cranio-facial and cranio-cervical dystonia symptoms. J Neurol. 2011 Nov;258(11):2069-74. doi: 10.1007/s00415-011-6075-0. Epub 2011 May 7. PMID: 21553081.
5)

Lyons MK, Birch BD, Hillman RA, Boucher OK, Evidente VG. Long-term follow-up of deep brain stimulation for Meige syndrome. Neurosurg Focus. 2010 Aug;29(2):E5. doi: 10.3171/2010.4.FOCUS1067. PMID: 20672922.

Knobloch syndrome

Knobloch syndrome

Knobloch syndrome (KS) is a rare autosomal recessive disorder associated with multiple ocular and cranial abnormalities. Occult occipital skull defect or encephalocele should raise suspicion of this disease. It is never reported in neurosurgical literature, possibly due to a lack of clinician familiarity, leading to underdiagnosis and inadequate management.

Four patients originally presented for genetic evaluation of symptomatic structural brain malformations. Whole-genome genotyping, whole-exome sequencing, and confirmatory Sanger sequencing were performed. Using immunohistochemical analysis, Caglayan et al. investigated the protein expression pattern of COL18A1 in the mid-fetal and adult human cerebral cortex and then analyzed the spatial and temporal changes in the expression pattern of COL18A1 during human cortical development using the Human Brain Transcriptome database.

They identified two novel homozygous deleterious frame-shift mutations in the COL18A1 gene. On further investigation of these patients and their families, they found that many exhibited certain characteristics of Knobloch syndrome, including pronounced ocular defects. This data strongly support an important role for COL18A1 in brain development, and this report contributes to an enhanced characterization of the brain malformations that can result from deficiencies of collagen XVIII.

This case series highlights the diagnostic power and clinical utility of whole-exome sequencing technology-allowing clinicians and physician scientists to better understand the pathophysiology and presentations of rare diseases. They suggest that patients who are clinically diagnosed with Knobloch syndrome and/or found to have COL18A1 mutations via genetic screening should be investigated for potential structural brain abnormalities even in the absence of an encephalocele 1).

Venkateshappa reported a patient that also had seizures, which is a sporadic presentation of this syndrome.

They report a clinico-radiologic finding of a 7-year-old boy who presented with seizures, cataracts, and an occipital bone defect along with bilateral subependymal heterotopias and polymicrogyria.

This case highlights the importance of consideration of this syndrome in children with a midline occipital bone defect with or without encephalocele and seizures. Early recognition of this presentation is critical for obtaining access to appropriate genetic counseling and subsequent monitoring and prevention of complications by surgical intervention 2).

References

1)

Caglayan AO, Baranoski JF, Aktar F, Han W, Tuysuz B, Guzel A, Guclu B, Kaymakcalan H, Aktekin B, Akgumus GT, Murray PB, Erson-Omay EZ, Caglar C, Bakircioglu M, Sakalar YB, Guzel E, Demir N, Tuncer O, Senturk S, Ekici B, Minja FJ, Šestan N, Yasuno K, Bilguvar K, Caksen H, Gunel M. Brain malformations associated with Knobloch syndrome–review of literature, expanding clinical spectrum, and identification of novel mutations. Pediatr Neurol. 2014 Dec;51(6):806-813.e8. doi: 10.1016/j.pediatrneurol.2014.08.025. Epub 2014 Sep 4. PMID: 25456301; PMCID: PMC5056964.
2)

Venkateshappa BM, Raju B, Rallo MS, Jumah F, Suresh SC, Gupta G, Nanda A. Knobloch Syndrome, a Rare Cause of Occipital Encephalocele and Seizures: A Case Report. Pediatr Neurosurg. 2021 Mar 31:1-5. doi: 10.1159/000512719. Epub ahead of print. PMID: 33789317.

Reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome (RCVS), AKA Call-Fleming syndrome, 1) a group of disorders sharing the cardinal clinical and angiographic features of reversible segmental multifocal cerebral vasoconstriction with severe headaches, focal ischemia, and/or seizures. May present as a hemorrhage restricted to a cortical sulcus

Epidemiology

RCVS has been reported to occur more frequently in women aged 20 to 50 years.

Etiology

Several mechanisms have been postulated involving transient deregulation of cerebral arterial tone, small vessel endothelial dysfunction, biochemical factors, hormonal deregulation, oxidative stress, and genetic predisposition. All these mechanisms and triggers are related with sympathetic over-activation which eventually produce vasoconstriction. RCVS is distinguished by acute severe recurrent thunderclap headaches with or without other neurological symptoms. However, the diagnosis can be challenging and most likely underdiagnosed requiring a high level of suspicion from the clinician 2).

Clinical features

Reversible cerebral vasoconstriction syndrome (RCVS) has emerged as the most frequent cause of thunderclap headache (TCH) in patients without aneurysmal subarachnoid hemorrhage, and as the most frequent cause of recurrent TCHs.

The typical TCHs of RCVS are multiple, recurring over a few days to weeks, excruciating, short-lived, and brought up by exertion, sexual activities, emotion, Valsalva maneuvers, or bathing, among other triggers. All these triggers induce sympathetic activation. In a minority of cases with RCVS, TCH heralds stroke and rarely death. Early diagnosis of RCVS in patients who present with isolated headache enables proper management and might reduce the risk of eventual stroke 3).

Outcome

Ischemic stroke affects nearly 25% of patients with RCVS and is associated with adverse clinical outcomes. RCVS patients with cerebrovascular risk factors might have a higher predisposition for developing ischemic lesions during the disease process 4).

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headache and diffuse segmental constriction of cerebral arteries that resolves spontaneously within a few months. Although manifestations of stroke are not included in diagnostic criteria of RCVS, it is known that some cases may be associated with stroke, including intracerebral hemorrhage, subarachnoid hemorrhage, or cerebral infarction.

Intracerebral hemorrhage is the most common vascular complication in hospitalized RCVS patients, resulting in longer hospitalizations with more invasive procedures and higher healthcare expenditure. However, overall outcomes are excellent regardless of types of ICH, with no inpatient mortality observed in patients with hemorrhagic RCVS. Female sex and middle to older age-group are associated with higher odds of ICH. 5).

Case series

162 patients with RCVS. Clinical, brain imaging, and angiography data were analyzed.

The mean age was 44±13 years, 78% women. Hemorrhages occurred in 43% including 21 patients with intracerebral hemorrhage (ICH) and 62 with convexal subarachnoid hemorrhage (cSAH). The frequency of triggers (eg, vasoconstrictive drugs) and risk factors (eg, migraine) were not significantly different between hemorrhagic and nonhemorrhagic RCVS or between subgroups (ICH versus non-ICH, isolated cSAH versus normal scan). Hemorrhagic lesions occurred within the first week, whereas infarcts and vasogenic edema accumulated during 2 to 3 weeks (P<0.001). Although all ICHs occurred before cSAH, their time course was not significantly different (P=0.11). ICH and cSAH occurred earlier than infarcts (P≤0.001), and ICH earlier than vasogenic edema (P=0.009). Angiogram analysis showed more severe vasoconstriction in distal versus proximal segments in all lesion types (ICH, cSAH, infarction, vasogenic edema, and normal scan). The isolated infarction group had more severe proximal vasoconstriction, and those with normal imaging had significantly less vasoconstriction. Multivariable analysis failed to uncover independent predictors of hemorrhagic RCVS; however, female sex predicted ICH (P=0.048), and angiographic severity predicted infarction (P=0.043).

ICH and cSAH are common complications of RCVS. Triggers and risk factors do not predict lesion subtype but may alter central vasomotor control mechanisms resulting in centripetal angiographic evolution. Early distal vasoconstriction is associated with lobar ICH and cSAH, and delayed proximal vasoconstriction with infarction 6).

Case reports

A rare case of RCVS in the setting of mild SARS-CoV-2 respiratory infection successfully treated with nimodipine and aspirin. SARS-CoV-2 attacks the Angiotensin-converting enzyme 2 receptors, which are expressed in various body organs including the lungs, kidneys, and blood vessels. Vasoconstriction can result from down-regulation of the ACE2-receptors that can lead to sympathetic hypertonia of the cerebral blood vessel walls and/or over-activation of the renin-angiotensin axis 7).

2018

Reversible Cerebral Vasoconstriction Syndrome Without Typical Thunderclap Headache Complicated by Intracranial Hemorrhage and Posterior Reversible Encephalopathy Syndrome:A Case Report 8).

Al-Mufti et al. from the Rutgers New Jersey Medical School, describe a case of medically refractory Reversible cerebral vasoconstriction syndrome (RCVS) that required treatment with intra-arterial (IA) verapamil and subsequent nimodipine, resulting in both angiographic and clinical improvement after failing to respond to hemodynamic augmentation.

They also supplement a description of the case with a review of other case studies and case series in which IA calcium channel blockers were used to treat RCVS. They propose that the case they outline demonstrates that neurointerventional management with IA verapamil is appropriate and effective as an early intervention of medically refractory RCVS.

Using PubMed and Google Scholar, they performed a search of the English language literature with several combinations of the keywords “intra-arterial”, “calcium channel blockers”, “reversible cerebral vasoconstriction syndrome”, “RCVS”, “nimodipine”, “verapamil”, “milrinone”, and “nicardipine” to identify studies in which RCVS was treated with IA calcium channel blockers.

They identified eight case studies and case series that met our inclusion criteria. Eighteen patients are encompassed in these eight studies.

IA administration of calcium channel blockers has been shown to return cerebral vessels to their normal caliber in patients with medically refractory RCVS. However, there are no randomized controlled trials of the treatment of RCVS, and further studies are needed to elucidate the optimal treatment protocol for medically refractory RCVS 9).

Gonsales et al., present an unusual case of an 18-year-old female who developed RCVS after embolization of a dural arteriovenous fistula with onyx embolic material. A cerebral angiogram was performed and verapamil was administered intra-arterially demonstrating slight improvement of the constricted vessels with clinical improvement. The patient was maintained on oral verapamil during hospitalization. At 7-month follow-up, the patient was neurologically stable and a cerebral angiogram demonstrated no signs of vasoconstriction.

Endovascular procedures are a rare trigger for the development of RCVS and may be misdiagnosed. Prompt recognition of symptoms and diagnosis with treatment are necessary to reduce the risk of stroke. The management should follow the premise of discontinuing precipitating drugs and administering CCBs 10).

2016

A 19-year-old woman had a thunderclap headache, followed by left hemiparesis and left homonymous hemianopsia. Laboratory tests showed no signs of infection and immunological test results were unremarkable. MRI revealed a cerebral infarction in the right posterior cerebral artery territory, and digital subtraction angiography(DSA)showed right posterior cerebral artery stenosis on day 2. The first follow-up DSA demonstrated an irregular, bead-like appearance on day 9, but the stenotic lesion returned to normal on day 21. Reversible cerebral vasoconstriction syndrome should be suspected in cases of rapid resolution of symptoms 11).

2014

Ishi et al. present three cases of RCVS associated with various types of stroke, and then review the literature. Case 1:A 49-year-old woman presented with a headache followed by left hemiparesis and dysarthria. One month before the onset, she was transfused for severe anemia caused by uterus myoma. CT images revealed intracerebral hemorrhages in the right putamen and right occipital lobe. Angiography revealed multiple segmental constrictions of the cerebral arteries. One month after the onset, these vasoconstrictions improved spontaneously. Case 2:A postpartum 38-year-old woman who had a history of migraine presented with thunderclap headache. Imaging revealed a focal subarachnoid hemorrhage in the right postcentral sulcus and segmental vasoconstriction of the right middle cerebral artery. One week after the onset, this vasoconstriction improved spontaneously. Case 3:A 32-year-old woman who had a history of migraine presented with headache followed by left homonymous hemianopsia. Imaging revealed a cerebral infarction of the right occipital lobe and multiple constrictions of the right posterior cerebral artery. These vasoconstrictions gradually improved spontaneously 12).

References

1)

Call GK, Fleming MC, Sealfon S, et al. Reversible cerebral segmental vasoconstriction. Stroke. 1988; 19:1159–1170
2) , 10)

Gonsales D, das Gracas F, Santos R, Aguilar-Salinas P, Hanel RA. Reversible Cerebral Vasoconstriction Syndrome as an Unusual Complication of a Dural Arteriovenous Fistula treated with Onyx Embolization. World Neurosurg. 2018 May 8. pii: S1878-8750(18)30931-8. doi: 10.1016/j.wneu.2018.04.211. [Epub ahead of print] PubMed PMID: 29751188.
3)

Ducros A, Wolff V. The Typical Thunderclap Headache of Reversible Cerebral Vasoconstriction Syndrome and its Various Triggers. Headache. 2016 Apr;56(4):657-73. doi: 10.1111/head.12797. Epub 2016 Mar 26. Review. PubMed PMID: 27015869.
4)

Garg A, Starr M, Rocha M, Ortega-Gutierrez S. Predictors and outcomes of ischemic stroke in reversible cerebral vasoconstriction syndrome. J Neurol. 2021 Mar 1. doi: 10.1007/s00415-021-10456-2. Epub ahead of print. PMID: 33646329.
5)

Patel SD, Topiwala K, Saini V, et al. Hemorrhagic reversible cerebral vasoconstriction syndrome: A retrospective observational study [published online ahead of print, 2020 Sep 7]. J Neurol. 2020;10.1007/s00415-020-10193-y. doi:10.1007/s00415-020-10193-y
6)

Topcuoglu MA, Singhal AB. Hemorrhagic Reversible Cerebral Vasoconstriction Syndrome: Features and Mechanisms. Stroke. 2016 Jun 7. pii: STROKEAHA.116.013136. [Epub ahead of print] PubMed PMID: 27272485.
7)

Mansoor T, Alsarah AA, Mousavi H, Khader Eliyas J, Girotra T, Hussein O. COVID-19 Associated Reversible Cerebral Vasoconstriction Syndrome Successfully Treated with Nimodipine and Aspirin. J Stroke Cerebrovasc Dis. 2021 Apr 12;30(7):105822. doi: 10.1016/j.jstrokecerebrovasdis.2021.105822. Epub ahead of print. PMID: 33895426.
8)

Miki K, Takemoto K, Morishita T, Kouzaki Y, Irie Y, Iwaasa M, Abe H, Inoue T. [Reversible Cerebral Vasoconstriction Syndrome Without Typical Thunderclap Headache Complicated by Intracranial Hemorrhage and Posterior Reversible Encephalopathy Syndrome:A Case Report]. No Shinkei Geka. 2018 Dec;46(12):1111-1115. doi: 10.11477/mf.1436203877. Japanese. PubMed PMID: 30572309.
9)

Al-Mufti F, Dodson V, Wajswol E, El-Ghanem M, Alchaki A, Nuoman R, Thabet A, Sutherland A, Roychowdhury S, Hidalgo A, Gupta G. Chemical angioplasty for medically refractory reversible cerebral vasoconstriction syndrome(). Br J Neurosurg. 2018 Sep 12:1-5. doi: 10.1080/02688697.2018.1479512. [Epub ahead of print] PubMed PMID: 30207193.
11)

Koh M, Tsuboi Y, Fukuda O. [A Case of Juvenile Cerebral Infarction due to Reversible Cerebral Vasoconstriction Syndrome]. No Shinkei Geka. 2016 Nov;44(11):965-969. Japanese. PubMed PMID: 27832620.
12)

Ishi Y, Sugiyama T, Echizenya S, Yokoyama Y, Asaoka K, Itamoto K. [Reversible cerebral vasoconstriction syndrome associated with stroke: three case reports]. No Shinkei Geka. 2014 Feb;42(2):129-36. Japanese. PubMed PMID: 24501186.

Pallidal Deep Brain Stimulation for Lance-Adams syndrome

Pallidal Deep Brain Stimulation for Lance-Adams syndrome

A 79-year-old woman presented with a history of cardiac arrest due to internal carotid artery rupture following carotid endarterectomy after successful cardiopulmonary resuscitation. However, within 1 month, the patient developed sensory stimulation-induced myoclonus in her face and extremities. Because her myoclonic symptoms were refractory to pharmacotherapy, deep brain stimulation of the GPi was performed 1 year after the hypoxic attack.

Continuous bilateral Pallidal Deep Brain Stimulation with optimal parameter settings remarkably improved the patient’s myoclonic symptoms. At the 2-year follow-up, her Unified Myoclonus Rating Scale score decreased from 90 to 24. In addition, Mure et al. observed burst firing and interburst pause patterns on intraoperative microelectrode recordings of the bilateral GPi and stimulated this area as the therapeutic target.

The results show that impairment in the basal ganglion circuitry might be involved in the pathogenesis of myoclonus in patients with Lance-Adams syndrome 1).

A 23-year-old male with chronic medication refractory PHM following a cardiopulmonary arrest related to an asthmatic attack who improved with bilateral globus pallidus internus (GPi) deep brain stimulation (DBS). Ramdhani et al. reviewed the clinical features of PHM, as well as the preoperative and postoperative Unified Myoclonus Rating Scale scores and DBS programming parameters in this patient and compare them with the three other published PHM-DBS cases in the literature.

This patient experienced an alleviation of myoclonic jerks at rest and a 39% reduction in action myoclonus with improvement in both positive and negative myoclonus with bilateral GPi-DBS. High frequency stimulation (130 Hz) with amplitudes >2.5 V were needed for the therapeutic response.

They demonstrated a robust improvement in a medication refractory PHM patient with bilateral GPi-DBS, and suggest that it is a viable therapeutic option for debilitating post-hypoxic myoclonus 2).

The first case of a patient who developed action myoclonus after experiencing perinatal anoxia and was successfully treated by chronic deep brain stimulation (DBS) of the thalamus (thalamic DBS).

The effectiveness of chronic thalamic DBS in this patient supports the concept of involvement of the thalamus in post-perinatal anoxic myoclonus 3).

Asahi T, Kashiwazaki D, Dougu N, et al. Alleviation of myoclonus after bilateral pallidal deep brain stimulation for Lance-Adams syndrome. J Neurol. 2015;262(6):1581-1583. doi:10.1007/s00415-015-7748-x 4).

Yamada K, Sakurama T, Soyama N, Kuratsu J. Gpi pallidal stimulation for Lance-Adams syndrome. Neurology. 2011;76(14):1270-1272. doi:10.1212/WNL.0b013e31821482f4 5).

References

1)

Mure H, Toyoda N, Morigaki R, Fujita K, Takagi Y. Clinical Outcome and Intraoperative Neurophysiology of the Lance-Adams Syndrome Treated with Bilateral Deep Brain Stimulation of the Globus Pallidus Internus: A Case Report and Review of the Literature [published online ahead of print, 2020 Sep 7]. Stereotact Funct Neurosurg. 2020;1-5. doi:10.1159/000509318
2) , 3)

Ramdhani RA, Frucht SJ, Kopell BH. Improvement of Post-hypoxic Myoclonus with Bilateral Pallidal Deep Brain Stimulation: A Case Report and Review of the Literature. Tremor Other Hyperkinet Mov (N Y). 2017;7:461. Published 2017 May 19. doi:10.7916/D8NZ8DXP
4)

Asahi T, Kashiwazaki D, Dougu N, et al. Alleviation of myoclonus after bilateral pallidal deep brain stimulation for Lance-Adams syndrome. J Neurol. 2015;262(6):1581-1583. doi:10.1007/s00415-015-7748-x
5)

Yamada K, Sakurama T, Soyama N, Kuratsu J. Gpi pallidal stimulation for Lance-Adams syndrome. Neurology. 2011;76(14):1270-1272. doi:10.1212/WNL.0b013e31821482f4

Foix-Chavany-Marie Syndrome case reports

Foix-Chavany-Marie Syndrome case reports

Demaerel R, Klein S, Van Calenbergh F. Syndrome of the Trephined presenting as Foix-Chavany-Marie syndrome [published online ahead of print, 2020 Jun 30]. Clin Neurol Neurosurg. 2020;196:106058. doi:10.1016/j.clineuro.2020.106058

Digby et al.from the Division of Neurosurgery, Addenbrooke’s Hospital, Cambridge, describes a case of a 62-year-old man who developed Foix-Chavany-Marie syndrome subsequent to traumatic brain injury. The initial presentation of the syndrome was profound loss of voluntary control of orofacial muscles, causing a loss of speech and impairment of swallow. Over subsequent months, a remarkable recovery of these functions was observed. The natural history of FCMS in this case was favourable, with good improvement in function over months. Furthermore, the pattern of bilateral opercular injury was more readily recognised on MRI than on CT, supporting the role of MRI in cases of traumatic brain injury 1).

Nitta et al.from the Department of Neurosurgery, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, reported a Foix-Chavany-Marie syndrome after unilateral anterior opercular contusion 2).

Martino et al. from the Department of Neurological Surgery, Hospital Universitario Marqués de Valdecilla and Instituto de Formación e Investigación Marqués de Valdecilla, Santander, reported a 25-year-old right-handed man with an incidentally diagnosed right frontotemporoinsular tumor who underwent surgery using an asleep-awake-asleep technique with direct cortical and subcortical electrical stimulation and a transopercular approach to the insula. While resecting the anterior part of the pars opercularis the patient suffered sudden anarthria and bilateral facial weakness. He was unable to speak or show his teeth on command, but he was able to voluntarily move his upper and lower limbs. This syndrome lasted for 8 days. Postoperative diffusion tensor imaging tractography revealed that connections of the pars opercularis of the right inferior frontal gyrus with the frontal aslant tract (FAT) and arcuate fasciculus (AF) were damaged. This case supplies evidence for localizing the structural substrate of FCMS. It was possible, for the first time in the literature, to accurately correlate the occurrence of FCMS to the resection of connections between the FAT and AF, and the right pars opercularis of the inferior frontal gyrus. The FAT has been recently described, but it may be an important connection to mediate supplementary motor area control of orofacial movement. The present case also contributes to our knowledge of complication avoidance in operculoinsular surgery. A transopercular approach to insuloopercular gliomas can generate FCMS, especially in cases of previous contralateral lesions. The prognosis is favorable, but the patient should be informed of this particular hazard, and the surgeon should anticipate the surgical strategy in case the syndrome occurs intraoperatively in an awake patient 3).

In 2013 Theys et al. from the Department of Neurosurgery, University Hospitals Leuven, reported a 48-year-old male patient recovering from complete anarthria after unilateral right-sided subcortical hemorrhagic stroke is described. The main outcome measures included clinical and neuroimaging data at three different time points (at the onset of symptoms, after 6 weeks and after 6 months). At 6 weeks, increased activations in the right and left frontal operculum were found and were followed by a trend towards normalization of the activation pattern at 6 months. These results suggest a role of anterior opercular regions in recovery from anarthria after subcortical stroke 4).

In 2009 Campbell et al. from the Department of Neurosurgery, Institute of Neurological Sciences, Southern General Hospital, Glasgow, presented a transient manifestation of the syndrome, in a patient who suffered two sequential traumatic brain injuries 5).

In 2006 Duffau et al. from the Department of Neurosurgery, Hôpital de la Salpêtrière, Paris reported in 42 patients a Foix-Chavany-Marie syndrome in 3 cases 6).

In 2003 they reported a 26-year-old right-handed man experienced partial seizures that were poorly controlled by antiepileptic drugs during a 2-year period as a result of a right insulo-opercular low grade glioma, leading to the proposal of surgical resection. In addition, 1 year before the operation, the patient experienced a severe brain injury that resulted in a coma. A computed tomographic scan revealed left opercular contusion. The patient recovered completely within 6 months.

Intraoperative corticosubcortical electrical functional mapping was performed along the resection, allowing the identification and preservation of the facial and upper limb motor structures. A subtotal removal of the glioma was achieved. The patient had postoperative anarthria, with loss of voluntary muscular functions of the face and tongue, and he had trouble chewing and swallowing. All of these symptoms resolved within 3 months.

These findings provide insight into the use of surgery to treat a right insulo-opercular tumor. First, surgeons must be particularly cautious in cases with a potential contralateral lesion (e.g., history of head injury), even if such a lesion is not visible on magnetic resonance imaging scans; preoperative metabolic imaging and electrophysiological investigations should be considered before an operative decision is made. Second, surgeons must perform intraoperative functional mapping to identify and to attempt to preserve the corticosubcortical facial motor structures. A procedure performed while the patient is awake should be discussed to detect the structures involved in chewing and swallowing in cases of suspected bilateral lesions. Third, the patient must be informed of this particular risk before surgery is performed 7).

A 10-year-old boy was brain injured in a traffic accident in August 1996. He was found comatous (initial GCS = 6) without any focal neurological deficit. The hemodynamic situation was stable even though he presented two wounds of the scalp and a hemoperitoneum that required intensive perfusions. The initial CT scan elicited a frontal fracture, ischemo hemorrhagic lesions of the right frontopolar and anterior temporal cortex. On the second day, he developed on the left side a subdural collection and a extradural hematoma which was surgically withdrawn. The comatous state ended on the ninth day. On examination, The child was awake and alert, able to understand spoken and written language but unable to speak. There was masticatory diplegia: the mouth was half open, the patient was drooling, chewing was impossible. The most striking feature was the automatic voluntary dissociation which might be observed on laughing, crying and yawning. The patient was unable to initiate swallowing but reflex swallowing was preserved once food was placed into the pharynx. The child had a deficit of voluntary control of muscles supplied by nerves V, VI, IX, X, XI. These clinical features are the hallmarks of SFMC. The first case was reported in 1837 by Magnus. The syndrome was described by Foix Chavany et Marie in 1926, and called SFMC by Weller (1993). His literature review of 62 SFMC allowed the differentiation of five clinical types: the classical and most common form associated with cerebrovascular disease, a subacute form caused by central nervous system infections, a developmental form, a reversible form in children with epilepsy and a rare type associated with neurodegenerative disorders. Bilateral opercular lesions was confirmed in 31 of 41 patients who had CT or MRI performed, and by necropsy in 7 of 10 patients. As previously reported, the outcome was poor for this boy who recovered very limited orofacial motor abilities. The medical functional readaptation was long et tedious and took in consideration the fact that the speech disturbance was anarthria and not an aphasic or an apraxic one and the age of onset of this acute acquired syndrome 8).

References

1)

Digby R, Wells A, Menon D, Helmy A. Foix-Chavany-Marie syndrome secondary to bilateral traumatic operculum injury. Acta Neurochir (Wien). 2018 Oct 17. doi: 10.1007/s00701-018-3702-x. [Epub ahead of print] PubMed PMID: 30328523.
2)

Nitta N, Shiino A, Sakaue Y, Nozaki K. Foix-Chavany-Marie syndrome after unilateral anterior opercular contusion: a case report. Clin Neurol Neurosurg. 2013 Aug;115(8):1539-41. doi: 10.1016/j.clineuro.2012.12.036. Epub 2013 Jan 28. PubMed PMID: 23369402.
3)

Martino J, de Lucas EM, Ibáñez-Plágaro FJ, Valle-Folgueral JM, Vázquez-Barquero A. Foix-Chavany-Marie syndrome caused by a disconnection between the right pars opercularis of the inferior frontal gyrus and the supplementary motor area. J Neurosurg. 2012 Nov;117(5):844-50. doi: 10.3171/2012.7.JNS12404. Epub 2012 Sep 7. PubMed PMID: 22957529.
4)

Theys T, Van Cauter S, Kho KH, Vijverman AC, Peeters RR, Sunaert S, van Loon J. Neural correlates of recovery from Foix-Chavany-Marie syndrome. J Neurol. 2013 Feb;260(2):415-20. doi: 10.1007/s00415-012-6641-0. Epub 2012 Aug 15. PubMed PMID: 22893305.
5)

Campbell E, St George EJ, Livingston A, Littlechild P. Case report of transient acquired Foix-Chavany-Marie syndrome following sequential trauma. Br J Neurosurg. 2009 Dec;23(6):625-7. doi: 10.3109/02688690902818841. PubMed PMID: 19922277.
6)

Duffau H, Taillandier L, Gatignol P, Capelle L. The insular lobe and brain plasticity: Lessons from tumor surgery. Clin Neurol Neurosurg. 2006 Sep;108(6):543-8. Epub 2005 Oct 6. PubMed PMID: 16213653.
7)

Duffau H, Karachi C, Gatignol P, Capelle L. Transient Foix-Chavany-Marie syndrome after surgical resection of a right insulo-opercular low-grade glioma: case report. Neurosurgery. 2003 Aug;53(2):426-31; discussion 431. PubMed PMID: 12925262.
8)

Laurent-Vannier A, Fadda G, Laigle P, Dusser A, Leroy-Malherbe V. [Foix-Chavany-Marie syndrome in a child caused by a head trauma]. Rev Neurol (Paris). 1999 May;155(5):387-90. Review. French. PubMed PMID: 10427603.

Intrathecal morphine for Restless Legs Syndrome

Intrathecal morphine for Restless Legs Syndrome

For those who suffer from a medically refractory Restless Legs Syndrome (RLS), intrathecal morphine treatment has been shown to be effective. The aim of a retrospective study of Steensland et al. was to investigate efficacy, complications and side effects in patients treated over several years with an implantable pump. A comparison was done to a group of patients treated with a similar pump system due to spasticity.

The charts of ten patients with severe or very severe RLS have been reviewed. These patients have received an intrathecal drug delivery system during 2000 -2016. To compare the rate of complications, a control group of 20 patients treated with intrathecal baclofen due to spasticity was included in the study. Their time of treatment corresponded to the RLS patients’.

The severity of symptoms related to RLS decreased significantly after treatment. Doses required ranged from 68 to 140 µg/day. Two cases of side effects were detected; one case with nausea and dizziness and one case with headache and fatigue. The rate of mechanical-, infectious- and other complications were similar between the two groups.

In light of the decrease in symptom severity and the low rate of side effects, intrathecal morphine can be considered an adequate treatment for those suffering from medically refractory RLS. The occurrence of complications did not differ between subjects with RLS and spasticity 1).

Case reports

Three patients with medically refractory RLS received an implanted pump for delivery of intrathecal morphine. Severity of RLS and self-assessed health were rated using the International Restless Legs Syndrome Study Group (IRLSSG) rating scale and the Short Form health survey (SF-36). Assessments were made preoperatively and after 6 months of follow-up.

Preoperatively two patients had very severe RLS, scoring 35 and 36 on the IRLSSG rating scale, and one patient had severe RLS (score, 26). All three patients were free of symptoms of RLS post-operatively and also at the 6-month follow-up. The daily doses of intrathecal morphine ranged from 73 to 199 µg. Results from the SF-36 health survey showed that all three patients had a better physical health compared to before surgery.

Intrathecal morphine may be efficient in the treatment for medically refractory RLS. All three patients became completely free of symptoms, and there was also improvement in self-perceived overall health 2)

In 2012 case reports of 4 patients documented excellent results with short-term use of intrathecal opioids also in RLS 3).

In 2008 Ross et al. reported the successful use of low-dose intrathecal morphine in a severe case of restless legs syndrome refractory to medication.

The surgery was complicated by extreme restlessness in the recovery room resulting in withdrawal or breakage of the catheter on multiple occasions. Relief of symptoms was lost with each catheter malfunction. They describes the possible origin of this complication and a solution to the problem resulting in the successful control of symptoms for 7 months since the last surgery. 4).

They are, however, wrong in their statement that this is the third published case of this particular treatment. In an article in the Swedish medical journal Lakartidningen 5), Lindvall et al. previously accounted for 7 patients with refractory restless legs syndrome who were successfully treated with intrathecal morphine. An abstract in English is available through the official web site of this journal, and the article is indexed by PubMed. The 7 patients were treated at 3 hospitals in the northern region of Sweden, which is covered by the neurosurgical department of Umeå University Hospital 6).

In 2002 two patients with incapacitating symptoms from restless legs syndrome, not adequately responding to conventional treatment with dopaminergic drugs, were implanted with a pump device (Isomed) for intrathecal delivery of morphine and bupivacaine. The treatment resulted in total resolution of all symptoms with few side effects 7).

References

1)

Steensland I, Koskinen LD, Lindvall P. Treatment of Restless legs with a pump; efficacy and complications. Acta Neurol Scand. 2019 Dec 28. doi: 10.1111/ane.13213. [Epub ahead of print] PubMed PMID: 31883387.
2)

Lindvall P, Hariz GM, Blomstedt P. Overall self-perceived health in Restless legs treated with intrathecal morphine. Acta Neurol Scand. 2013 Apr;127(4):268-73. doi: 10.1111/j.1600-0404.2012.01707.x. Epub 2012 Aug 9. PubMed PMID: 22881705.
3)

Hornyak M, Kaube H. Long-Term treatment of a patient with severe restless legs syndrome using intrathecal morphine. Neurology. 2012 Dec 11;79(24):2361-2. doi: 10.1212/WNL.0b013e318278b5e7. Epub 2012 Nov 28. PubMed PMID: 23197746.
4)

Ross DA, Narus MS, Nutt JG. Control of medically refractory restless legs syndrome with intrathecal morphine: case report. Neurosurgery. 2008 Jan;62(1):E263; discussion E263. doi: 10.1227/01.NEU.0000311089.04014.91. PubMed PMID: 18300885.
5)

Lindvall PK, Ruuth K, Jakobsson B, Nilsson SK. [Intrathecal morphine infusion a possible treatment in restless legs]. Lakartidningen. 2007 Aug 8-21;104(32-33):2250-2. Swedish. PubMed PMID: 17822205.
6)

Lindvall P, Ruuth K, Jakobsson B, Nilsson S. Intrathecal morphine as a treatment for refractory restless legs syndrome. Neurosurgery. 2008 Dec;63(6):E1209; author reply E1209. doi: 10.1227/01.NEU.0000325674.02282.CC. PubMed PMID: 19057291.
7)

Jakobsson B, Ruuth K. Successful treatment of restless legs syndrome with an implanted pump for intrathecal drug delivery. Acta Anaesthesiol Scand. 2002 Jan;46(1):114-7. PubMed PMID: 11903084.