Headache in stroke according to National Acute Stroke Israeli Survey.

OBJECTIVES: Analysis of headache occurrence in a national cohort of patients with acute stroke. METHODS: The data were based on the triennial 2-month period of the National Acute Stroke Israeli (NASIS) Registry. A total of 2166 patients with acute stroke were retrieved: 2001 (92.4%) had ischemic stroke (IS), 150 (6.9%) had intracerebral hemorrhage (ICH), 4 (0.2%) had sinus vein thrombosis (SVT), where as in 11 (0.5) the stroke type was undetermined. RESULTS: Two hundred and six (9.5%) patients reported headache: in SVT headache was reported by 50% of patients, in ICH by 21.3% while 8.4% of patients with IS (28% with transient ischemic attack [TIA]) complained about headache. In 18.1% of patients with headache, the stroke type was undetermined. Female gender, younger age, previous headache, cerebral hemorrhage, and dizziness/unsteadiness predisposed for headache. The incidence of headache was higher in patients with ICH than in patients with IS regardless of the history of previous headaches. In IS, headache decreased with stroke severity and was more common in the posterior than in the anterior circulation. Patients with lacunar stroke suffered less frequently from headache than patients with non-lacunar stroke. Significantly more patients with carotid dissection presented with headache than without. CONCLUSIONS: Intracerebral hemorrhage, younger age, female gender, posterior circulation involvement, and headache history are predictors for headache occurrence in acute stroke. Headache incidence in ICH correlates with stroke severity as opposed to IS. Headache in TIA is not unusual. Lacunar strokes are generally not accompanied by headaches. Headache remains the main complaint in SVT and carotid dissection.

Neurocognitive testing in late-onset Tay-Sachs disease: a pilot study.

OBJECTIVES: To test neurocognitive function in patients with late-onset Tay-Sachs disease (LOTS) using a computerized system to assess whether cognition is a clinically relevant outcome measure of possible therapeutic intervention in LOTS. METHODS: Ten adults with Tay-Sachs disease were administered at least one battery of the Mindstreams Neurotrax system for evaluation of cognitive function. Six sub-scores and a Global Cognitive Score (GCS) were tabulated. A disease specific severity score was also devised with six domains. RESULTS: Despite identical genotypes, all patients but the two oldest had > or = 3/6 sub-scores one standard deviation below normal mean (100); verbal and executive functions were most affected. The severity score measured other functions. CONCLUSIONS: Because of provocative findings on re-testing in patients exposed to miglustat, and despite the very small cohort, cognitive function may be an appropriate and clinically relevant outcome measure for future therapeutic interventions in LOTS.

Strokes after cardiac surgery: mostly right hemispheric ischemic with mild residual damage.

OBJECTIVE: Since cardiac surgery is now performed on patients with high risk for cerebrovascular disease, we studied the clinical findings and medium term outcome of patients with acute stroke/transient ischemic attack (TIA) after cardiac surgery. METHODS: All consecutive patients with acute stroke/TIA after cardiac surgery were prospectively observed during a 19 month period. Follow-up was between 3 months and 21 months. Risk factors, type of stroke, anatomic localization, initial neurological deficit and followup outcome were evaluated, using standard assessment scores. RESULTS: Among 406 patients operated (mean age 64.3 +/- 12.7 years, 284 males), 18 developed stroke and 2 TIAs (mean age 65.7 years, 13 males). There were no cases of intracerebral hemorrhage. Most of the strokes happened shortly after valve surgery (mean 1.3 days post operatively) and were right hemispheric (right = 11, left = 3; p = 0.034). Vertebrobasilar stroke appearance was delayed (mean: 8.25 days post operatively); they were attributed mostly to cardiac arrhythmias. Stroke/TIA patients did not have a higher preoperative risk than those without, but their cardiac functional score was worse (p = 0.01), and the average cardiopulmonary bypass time during surgery was longer (p = 0.009). Two patients died in hospital, both with vertebrobasilar stroke. Most of the hemispheric stroke patients became functionally independent (mean modified Rankin Scale < 2), even those with initial severe deficit. CONCLUSION: Strokes after cardiac surgery are mostly right hemispheric and exclusively ischemic. Outcome is relatively fair. We suggest an embolic injury to the right hemisphere, procedure related, as a possible mechanism.

Slowly progressive hemiparesis in childhood as a consequence of Rasmussen encephalitis without or with delayed-onset seizures.

Five young children developed slowly progressive hemiparesis as the initial manifestation of Rasmussen encephalitis (RE). Three have remained seizure free over an observational period of 1.3-1.9 years. In the remaining two patients, seizures occurred after 0.5 and 0.6 years respectively. We suggest that RE might be presently underdiagnosed and should be suspected in cases of new onset hemiparesis. In this series, three out of five patients showed oligoclonal bands on examination of cerebrospinal fluid (CSF) which represented additional diagnostic hints towards an immune-mediated condition. According to recently published formal diagnostic criteria, evidence of progressive cerebral hemiatrophy or bioptic identification of RE-typical inflammation confirms the diagnosis in such cases. Long-term immunotherapy is recommended in order to prevent further tissue loss and functional decline.

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Rasmussen encephalitis with active inflammation and delayed seizures onset.

Severe focal epilepsy is regarded as a clinical hallmark of Rasmussen encephalitis (RE). The authors report two children with progressive hemiparesis, contralateral hemispheric atrophy, and pathologic features characteristic for RE. At histologic diagnosis and over several months, neither patient experienced seizures. The report enlarges the clinical spectrum of RE and suggests that seizures are not an obligatory presenting symptom of the disorder.

MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If.

Deficiencies in the pathway of N-glycan biosynthesis lead to severe multisystem diseases, known as congenital disorders of glycosylation (CDG). The clinical appearance of CDG is variable, and different types can be distinguished according to the gene that is altered. In this report, we describe the molecular basis of a novel type of the disease in three unrelated patients diagnosed with CDG-I. Serum transferrin was hypoglycosylated and patients' fibroblasts accumulated incomplete lipid-linked oligosaccharide precursors for N-linked protein glycosylation. Transfer of incomplete oligosaccharides to protein was detected. Sequence analysis of the Lec35/MPDU1 gene, known to be involved in the use of dolichylphosphomannose and dolichylphosphoglucose, revealed mutations in all three patients. Retroviral-based expression of the normal Lec35 cDNA in primary fibroblasts of patients restored normal lipid-linked oligosaccharide biosynthesis. We concluded that mutations in the Lec35/MPDU1 gene cause CDG. This novel type was termed CDG-If.

Spinal cord involvement in uncomplicated herpes zoster.

We prospectively evaluated herpes zoster patients during the acute phase of the disease for central nervous system involvement. Of 24 patients with spinal zoster, 13 (54%) had spinal cord abnormality, which was asymptomatic in 12 of the 13. Age but not lack of acyclovir treatment was associated with such involvement. In all but 2, neurological involvement resolved within 6 months. Although the mechanism responsible for the neurological abnormalities is unknown, findings may support the hypothesis that zoster is associated with spread of viral infection into the spinal cord and therefore support the possibility that zoster is due to active viral replication in the ganglion.

Mutation in the methylenetetrahydrofolate reductase gene might be a risk factor for cerebrovascular disease in peripartum and under oral contraceptive use.

Nine women (age 22-43 years) with cerebrovascular diseases (CVD) related to pregnancy, puerperium or contraceptive use were studied. Five were pregnant, 2 were post partum and 2 were taking oral contraceptives. All under- went a complete etiological examination including assessment for the thermolabile C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene mutation. Three of the 9 patients were homozygotic for the C677T MTHFR mutation, and 3 were heterozygotic. In these 6 patients, no other etiology could be found. Mutation in the thermolabile MTHFR gene might be an important cause for CVD related to peripartum or contraceptive use.

Recurrent acute disseminated encephalomyelitis associated with acute cytomegalovirus and Epstein-Barr virus infection.

We describe a 5 6/12-year-old girl with recurrent episodes of acute disseminated encephalomyelitis following an acute cytomegalovirus infection and associated reactivated Epstein-Barr virus. Complete clinical recovery was obtained with intravenous immunoglobulin.

Muscular carnitine palmitoyltransferase II deficiency in infancy.

An 8-month-old female presented with febrile myoglobinuria. The activity of carnitine palmitoyltransferase (CPT) II was decreased to 16% of the control mean, and the oxidation of the long-chain fatty acids was reduced to 25% of the mean in the fibroblasts. Homozygosity for the common mutation, S113L, was identified in the CPT II gene. Residual CPT II activity of more than 10% of the mean and homozygosity for the common mutation S113L are usually associated with a milder reduction of long-chain fatty acid oxidation to about 80% of the control and with a later age of clinical onset. The early clinical presentation in the present patient is unique and was associated with a marked impairment of long-chain fatty acid oxidation, possibly because of other genetic factors. CPT II deficiency should be included in the differential diagnosis of isolated myoglobinuria in infancy.

Progressive dystonia with optic atrophy in a Jewish-Iraqi family.

The combination of progressive dystonia and optic atrophy is extremely rare and its morphological, metabolic and genetic basis is unknown. In a family of 9 children (8 males) born to consanguineous Israeli-Jewish-Iraqi parents, we identified four brothers who developed the syndrome at the end of the first decade. Patients had hemi or bilateral dystonia associated with striatal, mainly putaminal, atrophy on CT and MRI, various degrees of optic atrophy, minimal corticospinal tract involvement, normal intelligence and no peripheral nervous system or systemic abnormalities. No causative metabolic defect was identified. None of the several known mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy (LHON) or with LHON with dystonia were detected. Likewise, linkage to the idiopathic torsion dystonia region on chromosome 9q34 was excluded. It is suggested that this in our patients might be due to a yet unidentified genomic, autosomal recessive mutation.