Surgical treatment for epilepsy in 17 children with tuberous sclerosis-related West syndrome

The efficacy of surgery for the treatment of epilepsy in patients with West syndrome secondary to tuberous sclerosis is unclear. The charts of 17 patients with tuberous sclerosis and secondary West syndrome who underwent a one-stage surgical resection with a combined palliative operative procedure were reviewed. Engel classification was used to classify the patients with regard to seizure status following surgery. After surgery, 11 patients were in Engel class I, 4 in class II, and 2 in class III. The EEG after surgery was normal in 8 patients, significantly improved in 8, and without significant improvement in 1 patient. Six patients had a recurrence of seizures after surgery, which included 3 patients with continuing spasms and 3 patients where the spasms had resolved but had developed either partial seizures or generalized tonic-clonic seizures. There were significant improvements in the Gesell Developmental Schedules for motor field (P=0.003), adaptive field (P=0.003), language field (P=0.033), and personal-social field (P=0.007). Thus, a one-stage surgical approach can be used to produce satisfactory outcomes in young children with tuberous sclerosis who have secondary West syndrome and seizures that do not respond to conventional antiepileptic therapy, even in when there are multiple epileptogenic foci.     

Surgical treatment of myoclonus dystonia syndrome

Myoclonus dystonia (M‐D) syndrome is a heritable movement disorder characterized by myoclonic jerks and dystonia primarily of the upper extremities. M‐D remains poorly responsive to pharmacological treatment. Emerging reports suggest good response to DBS of the internal globus pallidus (GPi) and ventral intermediate nucleus (VIM) of the thalamus. This study aimed to appraise the value of these two DBS targets by evaluating reports available in the literature. A systematic search of published case reports and case series was performed on Medline and Embase. Responses to DBS were evaluated. Myoclonus was assessed with the Unified Myoclonus Rating Scale (UMRS) and dystonia by the Burke‐Fahn‐Marsden dystonia rating scale (BFMDRS). The primary outcome of interest was the relative improvements noted with GPi, compared to VIM stimulation. A total of 17 publications yielded 40 unique cases, with mean follow‐up of 27.2 months. All patients demonstrated improvements in myoclonus scores, with 93.5% showing at least a 50% improvement in UMRS. The mean improvement in myoclonus scores was 72.6%. In contrast, dystonia scores were improved in 87.9% of patients, with 72.7% reporting at least a 50% improvement in BFMDRS. The mean improvement in dystonia scores was 52.6%. Improvements in myoclonus scores were similar for both GPi (75.7%) and VIM (70.4%; P = 0.27). However, the improvements in dystonia scores were greater with GPi (60.2%), compared to VIM (33.3%; P = 0.03). Although both targets achieve similar improvements in myoclonus, GPi stimulation may be a preferred target because it may achieve greater improvements in dystonia, compared to VIM stimulation. © 2013 Movement Disorder Society     

Current treatment of West syndrome in Japan

About 10 years have passed since a previous survey on the treatment of West syndrome in Japan. To elucidate current practice, a questionnaire was sent to 113 institutes. It included (1) the drugs used for the treatment, (2) their dosage, and (3) the dosage and the schedule of adrenocorticotropic hormone therapy. Response rate was 51.3%. Adrenocorticotropic hormone, valproic acid, vitamin B(6), and zonisamide were frequently used. Vitamin B(6) was used most frequently as the first-choice drug followed by valproic acid, zonisamide, and adrenocorticotropic hormone. The most frequently used dose of synthetic adrenocorticotropic hormone-Z was 0.0125 mg/kg/d. Adrenocorticotropic hormone was administered every day for 2 weeks and then tapered off in more than 80% of the institutes. Although therapeutic strategy and drug usage have not changed largely during these 10 years, 2 alterations were observed: an increased use of zonisamide and a shortened duration of adrenocorticotropic hormone therapy.     

High-dose vitamin B(6) treatment in West syndrome.

Approximately 10-30% of patients with West syndrome respond to high-dose vitamin B(6) treatment. The response to vitamin B(6) is rapid; seizures disappear within the first 2 weeks of treatment. Mild side effects, such as gastrointestinal symptoms and liver dysfunction, are observed in 40-70%, but these resolve after discontinuation or a reduction of the dosage of vitamin B(6). High-dose vitamin B(6) treatment is useful as a first line agent in treating West syndrome.     

Zonisamide in West syndrome.

Zonisamide (ZNS), a new antiepileptic drug developed in Japan, is being used as the initial treatment of West syndrome in some Japanese institutes. The reported response rate varied from 20 to 38%. The cryptogenic patients showed a better response than the symptomatic patients. A striking finding was that the response to ZNS is rapid; most of the children who responded did so within 1-2 weeks of starting ZNS at a dose of 4-8 mg/kg/day. No serious side effects have been reported so far. ZNS may be both effective and well tolerated for the initial treatment of selected patients with West syndrome.     

儿童脊髓栓系综合征的手术治疗

目的探讨儿童脊髓栓系的临床特点、治疗方法、效果和预后。方法回顾性分析30例显微手术治疗的脊髓栓系病儿的临床资料。结果临床病理诊断：脂肪瘤型10例,非脂肪瘤型20例。术后随访O．5～4年,所有病儿局部皮肤包块和窦道畸形治愈,运动功能改善9例,感觉功能改善4例,二便功能改善5例。术后并发症：伤口愈合困难4例,新发小便困难1例,下肢麻木2例;1～3个月均恢复。所有病例无远期并发症。结论儿童脊髓栓系常合并先天畸形,多数病儿早期手术治疗能取得较好的预后。二便功能恢复较下肢感觉运动功能改善更为困难。     

Short-term nonhormonal and nonsteroid treatment in West syndrome

PURPOSE: West syndrome (WS) is considered an age-dependent epileptic encephalopathy and also a particular type of electrical epileptic status. Short-term hormonal or steroid treatment of WS with good efficacy is reported in the literature. The aim of this retrospective multiinstitutional study was to evaluate the early discontinuation of nonhormonal and nonsteroid treatment for WS. METHODS: Twenty-two WS cases in which treatment was discontinued after a maximum of 6 months, were collected. Inclusion criteria were the presence of typical EEG hypsarrhythmia (HY) and video-EEG recorded epileptic spasms. Exclusion criteria were the presence of partial seizures or other seizure types before spasm onset. The patients were treated with vigabatrin (VGB) in 19 cases and nitrazepam (NTZ) in three. The dose range was 70-130 mg/kg/day for VGB and 0.7-1.5 mg/kg/day for NTZ. The drug was discontinued if spasms stopped and HY disappeared after a mean treatment period of 5.1 months (range, 3-6 months). All patients underwent repeated and prolonged awake and sleep video-EEG, both before and after drug discontinuation. RESULTS: Cryptogenic (15) and symptomatic (seven) WS patients were included. All the symptomatic cases had neonatal hypoxic-ischemic encephalopathy. The mean age at spasm onset was 5.5 months (range, 3-7 months; median, 6). The interval between spasm onset and drug administration ranged from 7 to 90 days (mean, 23 days; median, 20). The interval between drug administration and spasm disappearance ranged from 2 to 11 days (mean, 6 days; median, 6 days). The interval between drug administration and HY disappearance ranged from 3 to 30 days (mean, 9 days; median, 10 days). Drugs were stopped progressively over a 30- to 60-day period. Follow-up ranged from 13 to 50 months (mean, 26 months; median, 22 months). None of our cases showed spasm recurrence. CONCLUSIONS: Our data show that successful nonhormonal and nonsteroid treatment can be shortened to a few months without spasm recurrence in patients with cryptogenic or postanoxic WS.     

Induced microseizures in West syndrome.

Induced microseizures (IMS) were observed in a 5-month-old girl with symptomatic West syndrome. The seizures occurred following the suppression of infantile spasms with adrenocorticotropic hormone therapy and disappeared following the cessation of clonazepam administration. The ictal manifestations consisted of periods of irregular respiration, and respiratory arrest lasting for several seconds which often involved opening of the eyes and mild extension of the neck corresponding with the diffuse fast wave bursts in EEG activity observed during sleep. These seizures were thought to be equivalent to the IMS in Lennox-Gastaut syndrome, which have never been reported before in patients with West syndrome.     

Sturge-Weber综合征的外科治疗：附1例报告

Sturge-Weber综合征 （ Sturge-Weber syndrome, SWS ）又称脑面血管瘤病（encephalofacial angiomatosis）或脑三叉神经血管瘤病（encephalotrigeminal angiomatosis），是一种罕见的以颜面和颅内血管瘤病为主要特征的先天性神经皮肤综合征。Sturge和Weber于1879年、1922年相继报道此病例。1936年，Bergstrand首次使用Sturge-Weber综合征这一名称，并由此命名。由于SWS发病率很低，因此对其诊断及治疗一直没有统一标准。本文报道了我科诊治的1例SWS，以探讨SWS外科治疗的术前评估及手术方法。     

Epidemiology of West syndrome in Singapore.

The incidence of West syndrome (WS) was determined by a search of reports of electroencephalograms (EEG) recorded in 1998 and 1999 in all public hospitals in Singapore. Amongst records of patients born in 1998, nine were found with EEG features of hypsarrhythmia or modified hypsarrhythmia with onset of seizures between January 1,1998 and December 31, 1999. The medical records of these patients were reviewed. The population of children born in 1998 was 43,664. In 1998 and 1999, 67% of all hospital admissions for patients 2 years or younger in Singapore were in public hospitals. The cumulative incidence of WS in Singapore corrected for the percentage of hospital admissions to public hospitals was 3.1/10,000 live births. The corrected cumulative incidences in Chinese, Malays and Indians were 2.7, 3.1 and 3.3 per 10,000, respectively. Three cases were idiopathic; three were due to congenital structural lesions of the brain; one each had periventricular leucomalacia, intracranial hemorrhage and severe intrauterine growth retardation. None of the patients were normal at follow up. The three patients with idiopathic WS had mild global developmental delay and the other six cases had cerebral palsy and severe mental retardation. With the best modern medical treatment, possibly only two of the nine cases of WS may have been prevented.     

Combined treatment with vigabatrin and topiramate in West syndrome

The clinical and electroencephalographic (EEG) response to combined therapy with vigabatrin and topiramate was evaluated in five patients ages 7 to 15 months affected by West syndrome in an open-label trial. Four patients had cryptogenic and one patient had symptomatic (tuberous sclerosis) West syndrome. In cryptogenic patients who failed to respond to pyridoxine, vigabatrin was titrated to 80 to 100 mg/kg. Because control of infantile spasms or an EEG improvement was not obtained with vigabatrin treatment, topiramate was added (3-3.8 mg/kg/day). In all patients, the combined therapy with topiramate and vigabatrin achieved a rapid and complete normalization of infantile spasms, and in three patients with cryptogenic West syndrome, the EEG also became normal. In only one patient, transient anorexia was observed. This drug combination led to rapid neurodevelopmental normalization in cryptogenic patients. The results are promising and justify more trials in larger numbers of children with West syndrome.     

West syndrome: the Philippine experience.

AIM: To provide information on the current status of West syndrome (WS) in the Philippines. METHODS: This is a retrospective review of WS cases from January 1997 to December 1999 from two largest referral government institutions. A questionnaire interview survey on anticonvulsant usage was also conducted among practicing child neurologists. RESULTS: Twelve patients diagnosed to have infantile spasms at 2-15 months were included, with a male:female ratio of 1:1. The proportion of WS cases among epileptic children under age 3 was 3.18%. The etiologies were idiopathic/cryptogenic in four (33%) and symptomatic in eight (66%). Symptomatic cases include hypoxic-ischemic encephalopathy, neonatal sepsis, bacterial meningitis, inborn error of metabolism, congenital brain anomaly and intracranial hemorrhage. Phenobarbital was the first line drug in 75% of cases. Other drugs used were valproic acid, clonazepam and pyridoxine. With a follow-up duration of 1-40 months, only three patients became seizure free and most had poor neurodevelopmental outcome. Among practicing child neurologists, the preferred ideal drug was adrenocorticotrophic hormone (ACTH) and valproic acid for idiopathic and symptomatic cases, respectively. However, in actual clinical practice valproic acid or prednisone was the initial drug used. Pyridoxine was usually added on. CONCLUSIONS: The proportion of WS in our patient population may not reflect the true prevalence in our country since our data came from a biased population, i.e. referral centers. A national statistics is currently not available. ACTH, which was perceived by most child neurologists as the ideal first line drug was not used primarily because it is unavailable and unaffordable. The poor seizure control and developmental outcome may be due to the treatment given or directly related to the etiology of WS.     

Thyrotropin-releasing hormone: role in the treatment of West syndrome and related epileptic encephalopathies.

Thyrotropin-releasing hormone (TRH) has been successfully used for treating children with neurologic disorders including epilepsy. The effectiveness of TRH and a TRH analog has been reported in West syndrome, Lennox-Gastaut syndrome, and early infantile epileptic encephalopathy that were intractable to anticonvulsants and adrenocorticotrophic hormone (ACTH). However, the peptide has not been widely studied as a treatment of intractable epilepsy outside Japan. TRH is safe in children and effective in some cases of West syndrome and Lennox-Gastaut syndrome. TRH is considered as a possible new strategy for treating West syndrome and Lennox-Gastaut syndrome prior to ACTH therapy, especially for the patient with an infection, immunosuppression, or severe organic lesions in the brain. The mechanisms of its antiepileptic action may differ from those of other antiepileptic drugs. One possibility is that TRH may act as an antiepileptic through a kynurenine mechanism, considering that kynurenic acid acts as an antagonist on the N-methyl-D-aspartate receptor complex.     

Surgical treatment of corneal pathology in patients with Down's syndrome

Keratoconus is a major cause of blindness in patients with Down's syndrome. A retrospective study of 30 corneal grafts for keratoconus in these patients revealed a 5-year graft survival of 67%. Postoperative trauma and/or infection was the main cause for graft failure. Conditions that should be met before the indication for corneal transplantation in a patient with Down's syndrome are formulated as a result of 15 years experience with that patient population. In appropriate cases, corneal transplantation may undoubtedly improve the quality of life in these patients.