Treatment of the West syndrome with high-dose pyridoxal phosphate

Fifteen (12.7%) among 118 cases of the West syndrome were effectively treated by high-dose pyridoxal phosphate (PAL-P). 1) Clinical seizures were completely suppressed in 12 cases with PAL-P alone, and in 3 cases by an addition of PAL-P to the previously poorly-effective regimen. At the follow-up, 12 cases have continued to be free from seizures, while two cases relapsed into the Lennox-Gastaut syndrome, and one died. 2) Electroencephalographically hypsarhythmia disappeared by PAL-P in all 15 effective cases. 3) Effective daily dose of PAL-P was 30 to 400 mg. 4) Notably, PAL-P was effective even in the cases with obvious organic brain pathology, such as tuberous sclerosis, porencephaly, holoprosencephaly, postmeningitis, besides 5 idiopathic cases. 5) Efficacy of PAL-P was significantly higher in idiopathic cases than symptomatic cases; 35.7% vs 9.6%. 6) Response to PAL-P was not predictable by any laboratory data nor clinical features. 7) Prognosis of PAL-P responsive cases was favorable; as many as 6 cases developed normally among 14 cases followed-up. Treatment with a high-dose PAL-P should be tried in all cases of the West syndrome at first.     

Cerebrospinal fluid somatostatin in West syndrome: changes in response to combined treatment with high-dose pyridoxal phosphate and low-dose corticotropin

Eighteen children with West syndrome (5–11 months of age) were selected to receive an oral dose of pyridoxal phosphate, (20–50 mg/kg) for 14 d. Seizures disappeared in one patient. The remaining 17 patients were treated with 0.01 mg/kg synthesized corticotropin intramuscularly for 2 weeks as an additional therapy. Seizures disappeared in all 17 patients within a few days after initiation of the corticotropin.Levels of somatostatin in the cerebrospinal fluid were as follows: 61.0 ± 10.7 pg/ml before therapy, 34.2 ± 6.4 pg/ml during pyridoxal phosphate therapy, and 26.8 ± 4.2 pg/ml after 2 weeks corticotropin therapy. Somatostatin levels in untreated patients were higher (p < 0.05) than those of age-matched controls (35.7 ± 11.8 pg/ml) and decreased (p < 0.05) after pyridoxal phosphate treatment. Somatostatin is a hypothalamic tetradecapeptide with excitatory effects on neurons and pyridoxal phosphate might subclinicaly influence neuronal excitation.     

Efficacy and safety of pyridoxal in West syndrome: A retrospective study

Objective

To evaluate the efficacy and safety of pyridoxal for treating West syndrome.

Biochemical studies of pyridoxal and pyridoxal phosphate status and therapeutic trial of pyridoxine in patients with carpal tunnel syndrome

A number of recent studies report response of patients with carpal tunnel syndrome to pyridoxine treatment. Neurological and biochemical studies were therefore performed on six patients both before and after treatment with pyridoxine for at least 9 weeks. Free pyridoxal, pyridoxal phosphate, and total pyridoxal were assayed in plasma and neutrophils. The pyridoxal status was also estimated by assaying red cell aspartate aminotransferase. No evidence was obtained to suggest that these patients were deficient in either pyridoxal or pyridoxal phosphate. Although four of the patients claimed some partial symptomatic relief, there was no consistent improvement in clinical findings or neurophysiological measurements following pyridoxine treatment.     

A successful electroconvulsive treatment of neuroleptic malignant syndrome

A case of neuroleptic malignant syndrome (NMS) treated successfully with electroconvulsive therapy (ETC) is described. Repeated exposures of the patients to succinylcholine during ECT did not cause malignant hyperthermia. The efficacy of ECT is probably related to its facilitatory effect upon dopamine (DA) activity in CNS.     

Tourette syndrome: successful treatment with clonidine and oxycodone

Summary A 15-year-old boy with Tourette's syndrome exhibited severe involuntary self-mutilatory behavior. While clonidine effectively controlled the motor and phonic tics, it failed to ameliorate the self-mutilatory behavior. Administration of oxycodone (50 mg/day) combined with clonidine produced a dramatic reduction in the frequency and severity of the self-mutilatory acts within 12 h. This report indicates that disturbances in the functional interplay between the noradrenergic and opiatergic systems may be important in the pathophysiology of Tourette's syndrome.     

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.     

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.     

Steroid-dependent form of Kinsbourne syndrome: successful treatment with trazodone

We report the case of a 19 month old girl with myoclonic encephalopathy of infants (MEI) (Kinsbourne syndrome), on long-term therapy with ACTH for the occurrence of frequent relapses (steroid-dependent form). The administration of trazodone per os at low doses as an alternative to the previous treatment ensured complete remission, also on the occasion of a subsequent relapse. No rebound effects were observed after trazodone withdrawal (10 months). At present, 3 years after withdrawal of the therapy, the child is well and free from symptoms. The hypothesis that trazodone may be effective in treating MEI, at least in cases that are steroid-dependent or resistant to ACTH, appears highly interesting. Trazodone is proposed as a possible alternative to treatment with ACTH.

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Sommario Viene segnalato il caso di una bambina di 19 mesi affetta da encefalopatia mioclonica infantile (EMI) (Sindrome di Kinsbourne), in trattamento cronico con ACTH per le frequenti recidive (forma steroido-dipendente).La somministrazione di trazodone per os, a basse dosi, in alternativa al trattamento precedente, ha consentito di ottenere la remissione completa, anche nel corso di una successiva ricaduta. La sospensione del trattamento (dopo 10 mesi) non si è associata a fenomeni di recidiva; attualmente, a 3 anni dalla sospensione, la bambina sta bene ed è libera da sintomi. Appare suggestiva l'ipotesi dell'efficacia del trazodone nella EMI, almeno in casi steroido-dipendenti o resistenti all'ACTH. Il trazodone viene proposto come possibile alternativa al trattamento con ACTH.

     

A successful treatment with intravenous lidocaine followed by oral mexiletine in a patient with Lennox-Gastaut syndrome]

Clusters of atypical absence, myoclonic seizures and tonic seizures developed in a thirteen-year-old boy with Lennox-Gastaut syndrome. As conventional antiepileptic drugs failed to eliminate the seizures, we treated the patient with continuous intravenous lidocaine (4 mg/kg/hr). The treatment reduced the duration of paroxysmal discharges (spike-wave complexes and rapid rhythm) from 3 sec/min to 0.7 sec/min, monitored by EEG. Oral mexiletine (5.4 mg/kg/day) following the lidocaine treatment has maintained good seizure control for two years with no adverse effects, and improved his behavioral problem. The treatment with lidocaine followed by mexiletine was useful for controlling clusters of intractable seizures.     

A case of Pallister-Killian syndrome associated with West syndrome

We report the case of a 19-month-old boy with Pallister-Killian syndrome associated with West syndrome. The child was born at term to a healthy mother after an uneventful pregnancy. He was born by cesarean section because of fetal macrosomia. He was observed to have nystagmus, craniofacial dysmorphism, and mental retardation. Intractable epileptic spasms developed 17 months after birth, and electroencephalography revealed a modified hypsarrhythmia. The seizures were uncontrollable with sodium valproate monotherapy. At the age of 19 months, the child was diagnosed with Pallister-Killian syndrome of mosaic tetrasomy 12p by fluorescence in situ hybridization. Combination treatment with high-dose pyridoxal phosphate and sodium valproate eliminated seizures and improved the electroencephalographic abnormalities. To our knowledge, this is the first reported case of Pallister-Killian syndrome associated with West syndrome.     

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.     

Surgical treatment of West syndrome.

The discovery of focal or multifocal cortical lesions using magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning in the majority of infants with West syndrome has led to a surgical approach in the treatment of some patients with intractable infantile spasms. The locations of these lesions should be concordant with localization of focal ictal and/or interictal electroencephalographic (EEG) abnormalities prior to proceeding with cortical resection. When a single lesion is present on the MRI or PET, and there is good correlation with EEG localization, surgical treatment is generally quite favorable in terms of both seizure control and cognitive development. Interictal glucose metabolism PET scans in children with intractable cryptogenic infantile spasms show unifocal cortical hypometabolism in about 20% of cases. In the majority, however, multifocal asymmetric hypometabolism is suggestive of multifocal underlying lesions, possibly multifocal cortical dysplasia. When the pattern of glucose hypometabolism is symmetric, a lesional etiology is less likely, thus neurometabolic or neurogenetic disorders should be considered. Therefore, the pattern of glucose hypometabolism on PET in infants with intractable cryptogenic spasms is a useful guide to decide whether a medical or surgical approach should be undertaken. In order to achieve the best cognitive outcome with surgery, it is important to resect the entire 'nociferous' area rather than just the seizure focus. Our research with new PET imaging probes has attempted to provide a comprehensive evaluation of the epileptogenic zone including the 'nociferous' cortex. We have used [(11)C]flumazenil (FMZ), which labels gamma aminobutyric acid(A) (GABA(A)) receptors, and have found this to be particularly useful in showing: (i) decreased receptor binding with medial temporal involvement thus indicating resection of medial temporal structures, (ii) the peri-lesional epileptogenic zone surrounding MRI lesions, (iii) the seizure onset zone in MRI-negative cases, and (iv) potential secondary epileptic foci. Another recently developed PET probe, alpha[(11)C]methyl-L-tryptophan (AMT) which is a precursor for the serotonin and the kynurenine metabolism pathways, is capable of differentiating between epileptogenic and non-epileptogenic tubers in patients with tuberous sclerosis complex and intractable epilepsy (including infantile spasms). Subsequently, we have applied AMT PET in patients with multifocal cortical dysplasia to determine the predominant seizure focus, and the results have been promising with regard to seizure control but not cognitive development. Thus, the introduction of newer more specific PET probes for epilepsy has led to improved and more accurate localization of seizure foci that should ultimately improve outcome of epilepsy surgery in West syndrome.     

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.     

Leigh syndrome associated with West syndrome

Leigh syndrome (LS) (sub-acute necrotizing encephalomyelopathy) is characterized by symmetric brain lesions occurring mainly in the basal ganglia and associated with variable clinical manifestations such as hypotonia, psychomotor retardation, and feeding difficulties. Patients with LS may develop seizures. Only three patients with LS have been identified in the literature as having West syndrome (WS). We have seen 12 children with LS in the past 20 years, and noticed that as many as five of them developed WS. This report discusses five LS children with WS, comparing them with seven LS children without WS. In all five patients, infantile spasms developed after LS had become evident, in addition to other type(s) of seizures. The onset of LS in all the patients with WS was before 10 months of age. Although not statistically proven, early onset of LS, spasticity, nystagmus, apnea, poor feeding, and cardiac problems seemed to be associated with the development of WS. We were not able to conclude that certain types of symptoms or examination results of patients with LS indicated the development of WS. The association of LS with WS did not markedly influence the prognoses of the children. WS may not be a rare complication of LS, especially in infants under 12 months of age. This report is the first review of LS associated with WS.     

Sequential MRI in chronic meningitis during adrenocorticotropic hormone treatment for West syndrome

I report a patient with West syndrome who suffered from chronic meningitis during adrenocorticotropic hormone treatment. The pleocytosis of cerebrospinal fluid continued, with vacillation, for more than 3 months. Sequential MRI studies with gadolinium contrast seem to be essential for evaluation of the activity and determination of the treatment in chronic meningitis.