Varicella Zoster Virus Cerebellitis Without a Rash in an Immunocompetent 85-Year-Old Patient.

BACKGROUND: Reactivation of the varicella zoster virus (VZV) in adults rarely presents with neurological symptoms without a rash. To our knowledge, so far, only 3 additional cases of VZV cerebellitis, which presented without a rash and were proven by cerebrospinal fluid analysis, have been reported in the literature. CASE REPORT: An immunocompetent 85-year-old patient presented with a new-onset tremor. He had no rash, had a normal brain computed tomography and magnetic resonance imaging, and had minimal cerebrospinal fluid findings. Eventually, he was diagnosed as having varicella zoster virus cerebellitis only on the basis of a virological examination. CONCLUSIONS: The manifestation of a new-onset tremor and gait ataxia should raise a suspicion of cerebellitis caused by VZV, even in the absence of cutaneous manifestations or typical imaging findings.

Incidence and risk factors of cerebrovascular events following cardiac catheterization.

BACKGROUND: One of the most daunting complications of cardiac catheterization is a cerebrovascular event (CVE). We aimed to assess the real-life incidence, etiology, and risk factors of cardiac catheterization-related acute CVEs in a large cohort of patients treated in a single center. METHODS AND RESULTS: We undertook a retrospective analysis of 43,350 coronary procedures performed on 30,907 procedure days over the period 1992-2011 and compared patient and procedural characteristics of procedures complicated by CVEs with the remaining cohort. CVEs occurred in 47 cases: 43 were ischemic, 3 intracerebral hemorrhages, and 1 undetermined. The overall CVE rate was 0.15%, with percutaneous coronary intervention (PCI) and diagnostic coronary angiography rates 0.23% and 0.09%, respectively. Using a forward stepwise multivariate logistic regression model including patient demographic and procedural characteristics, a total of 5 significant predictors were defined: prior stroke (OR=15.09, 95% CI [8.11 to 28.08], P<0.0001), presence of coronary arterial thrombus (OR=2.79, 95% CI [1.25 to 6.22], P=0.012), age >75 years (OR=3.33, 95% CI [1.79 to 6.19], P<0.0001), triple vessel disease (OR=2.24, 95% CI [1.20 to 4.18], P=0.011), and performance of intervention (OR=2.21, 95% CI [1.12 to 4.33], P=0.021). An additional analysis excluded any temporal change of CVE rates but demonstrated a significant increase of all high-risk patient features. CONCLUSION: In a single-center, retrospective assessment over nearly 20 years, cardiac catheterization-related CVEs were very rare and nearly exclusively ischemic. The independent predictors for these events were found to be the performance of an intervention and those associated with increased atherosclerotic burden, specifically older age, triple vessel disease, and prior stroke. The presence of intracoronary thrombus appears also to raise the risk of procedure-related CVE.

The relatively good outcome of cerebellum-brainstem ischemic strokes.

BACKGROUND: Our clinical experience suggests that the outcome of cerebellum-brainstem ischemic strokes is better than that of hemispheric ischemic strokes. METHODS: Within the setting of 2 national Israeli prospective stroke surveys, we analyzed risk factors, etiology, severity at presentation, and prognosis of first ischemic cerebellum-brainstem stroke (259 patients), comparing with strokes within the anterior circulation (1,029 patients). RESULTS: Patients with cerebellum-brainstem strokes were younger and had less frequently atrial fibrillation and congestive heart failure. Cardioembolic etiology was significantly less prevalent (p < 0.001). Severity at presentation was milder (p < 0.001). At discharge, worsening of the modified Rankin Scale was present in a smaller number of patients (p < 0.001); more returned to their home (p < 0.001). Six-month and 1-year mortality were lower (p < 0.001 for both). Adjusted logistic regression models showed that patients with cerebellum-brainstem strokes had 50% smaller chances of dying (OR 0.55; 95% CI 0.31-0.98) and a smaller chance of worsening of the modified Rankin Scale at discharge (OR 0.61; 95% CI 0.46-0.82). CONCLUSIONS: Cerebellum-brainstem strokes are less frequently cardioembolic, have a less severe presentation, and carry a better immediate and long-term prognosis.

D-serine adjuvant treatment alleviates behavioural and motor symptoms in Parkinson's disease.

Parkinson's disease (PD) manifestations include motor symptoms and behavioural deficits that resemble schizophrenia negative symptoms. The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) represents a novel pharmacological target in PD. D-serine (DSR) allosterically modulates in-vivo NMDAR-mediated neurotransmission and has been shown to improve negative and antipsychotic drug-induced parkinsonian symptoms in schizophrenia patients. This pilot study assessed DSR effects in ten PD patients who completed a 6-wk double-blind, placebo-controlled, crossover adjuvant treatment trial with 30 mg/kg.d DSR. Primary outcome analyses consisted of separate repeated-measures multivariate analyses of variance for Unified Parkinson's Disease Rating Scale (UPDRS), Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), Abnormal Involuntary Movement Scale (AIMS), and Positive and Negative Syndrome Scale (PANSS) scores. DSR treatment was well tolerated and resulted in increased DSR serum levels (p=0.001) and significantly reduced UPDRS (p=0.02), SAS (p=0.009) and PANSS (0.05) total scores. These preliminary findings suggest that DSR treatment may be beneficial in PD. Larger-sized studies with optimized DSR dosages are warranted.

No symptomatic intracerebral hemorrhage after cardiac surgery: a 14-year retrospective study.

BACKGROUND: In the presence of new neurological findings occurring after cardiac surgery, the clinical question is whether to exclude symptomatic intracerebral hemorrhage (ICH), particularly in the context of routine postoperative anticoagulation treatment. METHODS: This is a retrospective 14-year study including 5,275 patients who underwent cardiovascular surgery. The control cohort included all patients with acute cerebrovascular accidents hospitalized in 2 general hospitals in Jerusalem during a 2-month period in 2007 (part of a national survey). RESULTS: After cardiac surgery, 78 patients developed ischemic strokes, mostly of large-vessel etiology. These ischemic strokes occurred more often in patients who underwent combined operations (22/647 = 3.4% vs. 45/3,489 = 1.3%; p = 0.0004). ICH was found in 6% of all acute cerebrovascular accidents in the general survey, but was absent after cardiac surgery (5 vs. 0; p = 0.02). CONCLUSIONS: Despite hypertension as a main risk factor and the administration of postoperative anticoagulation, we found that symptomatic ICH did not occur after cardiac surgery.

The possible risk for strokes complicating cardiac surgery in patients with intraoperative hypothermia.

BACKGROUND: The effect of hypothermia as a possible neuroprotective tool on the outcome of cardiac surgery is still controversial. METHODS: We retrospectively assessed all patients who underwent cardiac surgery within a 14-year period and compared patients with and without postoperative stroke. RESULTS: Stroke occurred more frequently in patients who underwent valve repair/replacement combined with coronary artery bypass grafting (CABG) than in patients who had CABG alone (p = 0.0002). All strokes (1.4%) were ischemic and mostly of large-vessel etiology. All patients with stroke had intraoperative minimal temperature <34°C. More patients in this group than in the group without stroke had an intraoperative minimal temperature <30°C (p = 0.01). Stepwise multivariate analysis of all pre- and intraoperative parameters identified significant risk factors for stroke: hypertension, diabetes mellitus and previous stroke as preoperative risk factors, but only lower minimal temperature as a significant intraoperative risk factor (p = 0.03; odds ratio 1.080/1°C, 95% confidence interval 1.004-1.152). The mean intraoperative temperature was 28 ± 4°C in patients who developed stroke and 30 ± 3°C in patients without stroke. CONCLUSIONS: Intraoperative hypothermia around 28°C might be harmful and associated with increased risk for postsurgical stroke.

Reaction to intravenous contrast media mimicking intracerebral hemorrhage after percutaneous coronary intervention.

BACKGROUND: Cerebroavascular complications after percutaneous coronary interventions, although rare, need immediate diagnostic and treatment in order to minimize the possible sequelae. CASE REPORT: At the end of a percutaneous coronary intervention a 63-year old man, long standing migraineur, developed severe headache, confusion, nausea, photophobia, slow speech and left hemiparesis. In the presence of hyperdensity of the right parietal area in the brain CT, he was suspected to suffer from intracerebral hemorrhage, and treatment with platelet glycoprotein IIb/IIIa inhibitors was immediately stopped. Revision of the CT and disappearance of the clinical and radiological signs were concordant with the diagnosis of intraparenchymal extravasation of the contrast media. CONCLUSIONS: We report a very rare complication of contrast media after coronary angiography with extravasation unilaterally in the anterior circulation. Recognition of this complication can avoid unnecessary investigations.

DSM-IV combined type ADHD shows familial association with sibling trait scores: a sampling strategy for QTL linkage.

Attention deficit hyperactivity disorder (ADHD) is a discrete clinical syndrome characterized by the triad of inattention, hyperactivity, and impulsivity in the context of marked impairments. Molecular genetic studies have been successful in identifying genetic variants associated with ADHD, particularly with DSM-IV inattentive and combined subtypes. Quantitative trait locus (QTL) approaches to linkage and association mapping have yet to be widely used in ADHD research, although twin studies investigating individual differences suggest that genetic liability for ADHD is continuously distributed throughout the population, underscoring the applicability of quantitative dimensional approaches. To investigate the appropriateness of QTL approaches, we tested the familial association between 894 probands with a research diagnosis of DSM-IV ADHD combined type and continuous trait measures among 1,135 of their siblings unselected for phenotype. The sibling recurrence rate for ADHD combined subtype was 12.7%, yielding a sibling recurrence risk ratio (lambda(sib)) of 9.0. Estimated sibling correlations around 0.2-0.3 are similar to those estimated from the analysis of fraternal twins in population twin samples. We further show that there are no threshold effects on the sibling risk for ADHD among the ADHD probands; and that both affected and unaffected siblings contributed to the association with ADHD trait scores. In conclusion, these data confirm the main requirement for QTL mapping of ADHD by demonstrating that narrowly defined DSM-IV combined type probands show familial association with dimensional ADHD symptom scores amongst their siblings.

Sydenham's chorea in Jerusalem: still present.

BACKGROUND: In developed countries the incidence of Sydenham's chorea, a major sign of rheumatic fever, has declined, but outbreaks are still encountered worldwide. OBJECTIVES: To report the characteristics of a cohort of SC patients in the Jerusalem area. METHODS: We conducted a prospective assessment of rheumatic fever and SC between 1985 and 2002. The diagnosis of rheumatic fever was based on the revised Jones criteria. Other etiologies of chorea were excluded. Recurrence was defined as the development of new signs lasting more than 24 hours and separated by a minimum of 2 months from the previous episode. Patients were followed for 1 to 14 years following the initial SC episode, and at least one year after recurrence. RESULTS: Among 180 children with rheumatic fever, 24 had SC. Most of them came from large families of Ashkenazi origin. In 19 patients (79%) the chorea was associated with other rheumatic fever signs, while 5 had pure chorea. Due to the systematic use of two-dimensional color Doppler echocardiography, cardiac involvement was detected in 75% of the patients. Ten patients (42%, 7 females) developed 11 recurrent episodes of chorea 3 months to 10 years after the initial episode. At recurrence, chorea was the sole rheumatic sign in all nine patients who recurred once. None of the patients had persistent chorea. CONCLUSIONS: SC is still prevalent in the pediatric population of Jerusalem, and may recur years later. Recognition of the disease and adequate treatment is necessary.

Recurrence of Sydenham chorea: implications for pathogenesis.

BACKGROUND: Sydenham chorea (SC), a major sign of rheumatic fever (RF), is related to systemic streptococcal infection and is treated with antibiotics. Recurrence usually occurs within a short interval following the initial event and is considered part of RF. OBJECTIVE: To evaluate the rate, nature, and course of recurrent SC during an extended follow-up period. DESIGN: Prospective assessment of a cohort of patients with SC who were admitted between 1985 and 2002. SETTING: General community hospital. METHODS: Diagnosis of RF was based on the revised Jones criteria. Other causes of chorea were excluded. Recurrence was defined as the development of new signs, lasting more than 24 hours and separated by a minimum of 2 months from the previous episode. Patients were observed from 1 to 14 years following the initial SC episode and for at least 1 year after recurrence. At recurrence, patients were assessed for RF clinical and laboratory activity, including change in cardiac involvement. RESULTS: Twenty-four patients had SC. In 19 patients (79%), the chorea was associated with other RF signs, and 5 suffered from pure chorea. Ten patients (42%, 7 women) developed 11 recurrent episodes of chorea 3 months to 10 years after the initial episode. Association of recurrent chorea with RF could be suspected in only 6 episodes: cessation of prophylactic antibiotic treatment or poor compliance in 4 patients and rise in antistreptolysin O titers in 2. In an 18-year-old woman, chorea recurred during her first pregnancy. At recurrence, chorea was the sole rheumatic sign in all 9 patients who had 1 recurrent episode. In the patient with 2 recurrent episodes, mitral regurgitation developed into mitral stenosis. No statistical differences in previous RF activity and rheumatic cardiac involvement between patients with recurrent SC and patients with a single episode could be found. CONCLUSIONS: In a significant subgroup of patients, SC recurrence might not be a true relapse of rheumatic fever. It might represent either a primary underlying abnormality that renders patients susceptible to developing such a movement disorder or the outcome of permanent subclinical damage to the basal ganglia following the initial SC episode.

Complete mitochondrial DNA sequence analysis in a family with early-onset dystonia and optic atrophy.

The combination of optic atrophy and dystonia has been etiologically associated with mitochondrial DNA (mtDNA) mutations. We report here on the complete mtDNA sequence from the proband of a consanguineous family exhibiting "mitochondrial-like" optic atrophy and dystonia. A candidate tRNA(Gly) mutation was identified that was unique to the family. However, the mutation was homoplasmic in both affected and unaffected family members and we were unable to demonstrate a biochemical defect in patient mitochondria. Hence, it is unlikely that a mtDNA mutation accounts for the phenotype in this family.

Early peripheral nervous system manifestations of infantile Krabbe disease.

Early infantile Krabbe disease is relatively frequent in the Muslim-Arab population in Israel. It can be easily diagnosed when it presents with the classic clinical picture characterized by central nervous system manifestations of spasticity, irritability, motor regression and seizures associated with a positive family history. We studied eight children diagnosed with Krabbe disease. In two of these children (25%), peripheral neuropathy was the single initial symptom and the only neurologic finding noted for a period of months. In these patients, diagnosis of Krabbe's disease was delayed and established only 9-11 months after the initial symptoms. In two other children with "classical picture" Krabbe disease, areflexia was noted on admission. The occurrence of peripheral neuropathy as an initial symptom in early infantile Krabbe disease may be underestimated. Krabbe disease should be considered in the differential diagnosis of early infantile peripheral neuropathy. Early diagnosis of affected children might be important for genetic counseling for families at risk.