The neuropsychological profile of patients with 3-methylglutaconic aciduria type III, Costeff syndrome.

Costeff syndrome is a rare genetic neuro-ophthalmological syndrome consisting of early-onset bilateral optic atrophy along with a progressive complex motor disorder with elevated levels of urinary 3-methylglutaconic acid and 3-methylglutaric acid. While borderline to mild cognitive deficits have been considered to be common in patients with this syndrome, a comprehensive cognitive assessment has never been performed. The aim of the current study was to explore the cognitive profile associated with Costeff syndrome. Sixteen adult patients diagnosed with Costeff syndrome were administered a neuropsychological test battery that was composed of standardized verbal tests adapted for the blind. General intelligence ranged from average to borderline, with a group mean consistent with intact general cognitive functioning (VIQmean = 85, z = -1) in the low-average range of the general population. The auditory immediate and delayed memory indexes were in the average range and were significantly higher than the general cognitive functioning, whereas the working memory index was significantly lower than the general cognitive functioning. Adult patients with Costeff syndrome have intact global cognition and learning abilities and strong auditory memory performance. © 2015 Wiley Periodicals, Inc.

Exploring determinants of progression in Parkinson's disease. Is there a difference among Jewish ethnic groups?

INTRODUCTION: Parkinson's disease (PD) displays an individually variable rate of progression, of which the underlying mechanisms are largely unknown, but may involve genetic factors. In this study, we aimed to explore the effect of ethnic origin on PD progression rate in Israeli Jews, as expressed by time from onset until reaching Hoehn and Yahr stage 3 (HY3). METHODS: Consecutive patients with PD followed bi-annually at the Movement Disorders Institute at Sheba Medical Center, were included. Demographic data and clinical information, including age at PD onset (AO), H&Y staging, and family history of PD, were collected. Ethnicity was determined based on the parents' origin and was categorized as Ashkenazi Jews (AJ), Yemenite Jews (YJ), North African Jews (NAJ) and Oriental Jews (OJ) excluding YJ. Associations between the above variables and the time to HY3 were determined using Cox proportional hazards model. Survival curves were derived from the model. RESULTS: Of 707 patients [430 males, AJ: 458, YJ: 37, NAJ: 75 and OJ: 137] included in the analysis, 343 had reached HY3. In a multivariate analysis, a longer time to HY3 was significantly associated with a younger AO (HR = 1.07, p < 0.001). YJ showed a significantly shorter time to HY3 compared to AJ and OJ, but not compared to NAJ. Time to HY3 was significantly shorter for NAJ than for OJ. CONCLUSION: Jewish PD patients of Yemenite and North African origin may have a more rapid progression of PD, compared to those of Ashkenazi and Oriental origin, suggesting distinctive genetic influences.

Neurologic and other systemic manifestations in FMF: published and own experience.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease, presenting with recurrent episodes of fever and polyserositis. Neurologic involvement in FMF is rare and usually considered fortuitous. The aim of this article is to review the spectrum of possible neurologic manifestations, which can be encountered in FMF patients, and to establish their relation to FMF. METHODS: We reviewed the literature based on Pubmed search to find neurologic manifestations, which were reported in FMF patients. To that we added our own experience on the subject, abstracted from our computerised FMF registry of 12000 FMF patients of the National FMF Center and the computerised database of Sheba Medical Center. RESULTS: A wide range of neurologic manifestations involving FMF patients was noted. A large part of these manifestations could be directly related to FMF, its complications, associated diseases and treatment adverse effects. The remaining were incidental, or of uncertain association to FMF. CONCLUSION: A physician, taking care of an FMF patient, can face various neurologic manifestations and should be aware of their origin. The current chapter provides an insight to this association of FMF.

Familial Mediterranean fever (FMF) and multiple sclerosis: an association study in one of the world's largest FMF cohorts.

BACKGROUND AND PURPOSE: To describe and characterize the association between familial Mediterranean fever (FMF) and multiple sclerosis (MS). METHODS: The patient registry of The National Center for FMF was screened for the coexistence of FMF and MS. Tel-Hashomer criteria were used for the diagnosis of FMF, and FMF severity was evaluated, using the simplified FMF severity scale. McDonald criteria were used for the diagnosis of MS, and neurologic disability was measured using the expanded disability status scale (EDSS). RESULTS: We identified nine patients, affected with both FMF and MS. The onset of the FMF averaged 15.6 (3-37) years. Most patients suffered from abdominal and joint attacks, and 50% of the patients sustained a moderate to severe FMF. The onset of the MS was at an average age of 31.6 (17-50) years. Neurologic manifestations varied individually, without a dominant deficit, and the course was in a relapsing-remitting pattern in most. The median EDSS was in general of low score (3.0), apart from the patients who were homozygous for the M694V mutation, in whom the MS was more severe. Based on our case series, the frequency of MS in our FMF population is 0.075%, twice higher the expected rate in the general population (P=0.0057). CONCLUSIONS: Multiple sclerosis is more common in FMF than in the general Israeli population. Homozygosity for the M694V MEFV mutation may aggravate the phenotype of MS and predispose FMF patients to develop MS.

Epilepsy syndrome-associated balance dysfunction assessed by static posturography.

PURPOSE: To compare subclinical balance dysfunction in patients with various epilepsy syndromes with apparently healthy subjects. METHODS: Twenty-seven patients with localization-related epilepsy (LRE), 19 with primary generalized epilepsy (PGE), who had no subjective complaints of impaired balance and no abnormal neurologic findings on examination, and 22 apparently healthy subjects, underwent static posturography using the Posture Scale Analyzer (PSA) system. RESULTS: Sway index was higher in patients compared to healthy subjects in all tests, significant for single leg stance (p=0.005). Patients with PGE had a higher sway index compared to patients with LRE in six of the tests, also significant for single leg stance (p=0.027). This difference was not affected by the type of AED treatment or disease duration. CONCLUSION: Posturography can improve balance function assessment in patients with epilepsy, demonstrate subclinical impairment in seemingly asymptomatic patients, and further characterize balance deficits in different epilepsy syndromes.

Internal obturator muscle abscess caused by Klebsiella pneumoniae.

Obturator internus muscle abscess is an infrequent form of pyomyositis. To date, this disease has been described almost exclusively in children and young adults, and in most cases the causative agents are Gram-positive bacteria. We present the first report of obturator internus muscle abscess caused by a highly antibiotic resistant Klebsiella pneumoniae, in an elderly diabetic patient. Once considered very rare, Gram-negative pyomyositis is increasingly reported, and is an important concern in diabetic patients. Since pyomyositis can easily be missed if not considered, physicians should become familiar with this condition, and consider it in the differential diagnosis of septic diabetic patients.

Hand rhythmic tapping and timing in Parkinson's disease.

BACKGROUND: Dysrhythmia is one of the features frequently associated with the motor disturbance in Parkinson's disease (PD). The mechanism responsible for this phenomenon is not known. OBJECTIVES: To assess the rhythmic movements of the hand in PD patients in general and in parkinsonian subtypes. METHODS: Fifty-one PD patients (32 males) with mean age 66.3 +/- 9.1 years (6.6 years of symptoms) and 36 healthy controls (age 64.9 +/- 13.2, range 40-85) were studied. Subjects were asked to tap with their dominant or less affected arm on a digitized switch board at their most comfortable pace (16 s), fastest tapping speed (12 s), and at different frequencies provided by a metronome. The mean rhythm and the tap-to-tap variation were compared. Performance of the PD patients and control subjects were compared, as there were different subtypes of PD patients. Patients were subclassified into: tremor predominant (TP) (14 patients), freezing predominant (FP) (11 patients), akinetic-rigid (AR) (12 patients) and an unclassified group (UC) (14 patients). Results. There was no significance difference between patients and controls in the self-chosen, most comfortable tapping rate or in the tap-to-tap variation of the self-paced task. PD patients tapped at a significantly slower rate than controls when asked to tap at their fastest rate (4.39 +/- 1.32 vs. 5.14 +/- 1.31 Hz; p < 0.01). This difference was the result of an especially slow performance of the TP and AR subgroups (3.85+/-1.20 and 3.88+/-1.46, respectively; p < 0.01 compared to the control group). TP was the only subgroup to show an increased tap-to-tap variation at their fastest tapping rate compared to the control group (0.070 +/- 0.057 vs. 0.029 +/- 0.025 s, respectively, p < 0.05). The TP subgroup also showed hastening when they followed an externally given rhythm of 2.5 Hz and they tapped at 2.73 +/- 0.36 Hz p < 0.05). CONCLUSIONS: Externally driven and self-paced tapping are preserved in patients with PD, when examined at their best 'on' state. The tremor predominant subgroup seems to have specific pacing disturbances.

Reducing the flexibility of retinal restores a wild-type-like photocycle in bacteriorhodopsin mutants defective in protein-retinal coupling.

The thermal re-isomerization of retinal from the 13-cis to the all-trans state is a key step in the final stages of the photocycle of the light-driven proton pump, bacteriorhodopsin. This step is greatly slowed upon replacement of Leu-93, a residue in van der Waals contact with retinal. The most likely role of this key interaction is that it restricts the flexibility of retinal. To test this hypothesis, we have exchanged native retinal in Leu-93 mutants with bridged retinal analogs that render retinal less flexible by restricting free rotation around either the C10-C11 (9,11-bridged retinal) or C12-C13 (11,13-bridged retinal) single bonds. The effect of the analogs on the photocycle was then determined spectroscopically by taking advantage of the previous finding that the decay of the O intermediate in the Leu-93 mutants provides a convenient marker for retinal re-isomerization. Time-resolved spectroscopic studies showed that both retinal analogs resulted in a dramatic acceleration of the photocycling time by increasing the rate of decay of the O intermediate. In particular, exchange of native retinal in the Leu-93 --> Ala mutant with the 9,11-bridged retinal resulted in an acceleration of the decay of the O intermediate to a rate similar to that seen in wild-type bacteriorhodopsin. We conclude that the protein-induced restriction of conformational flexibility in retinal is a key structural requirement for efficient protein-retinal coupling in the bacteriorhodopsin photocycle.