An assessment of Movement Disorder Society Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease.

BACKGROUND AND PURPOSE: Cognitive impairment is one of the most disabling non-motor symptoms of Parkinson's disease. Mild cognitive impairment constitutes a major risk for the development of Parkinson's disease dementia in the course of the disease. A Movement Disorder Society Task Force proposed diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD-MCI), comprising two operational levels: Level I and Level II. The objective of our study was to test the accuracy of Level I versus Level II diagnostic criteria. METHODS: Eighty-six consecutive patients with Parkinson's disease were screened and 68 patients without dementia or depression were included in the study. We used the Montreal Cognitive Assessment, Mini-Mental State Examination and Addenbrooke's Cognitive Evaluation-R screening tools for Level I and an extensive neuropsychological battery for Level II assessment. We first diagnosed PD-MCI on the basis of Level II assessment and then calculated sensitivity, specificity and area under the receiver-operator characteristics curve, comparing the performance of the three screening batteries. RESULTS: None of the three screening batteries proposed for Level I assessment provided satisfactory combined sensitivity and specificity for detecting PD-MCI, and their performance was similar. Using the Level II criteria, 29 patients (43%) were diagnosed as having PD-MCI. Lowest cut-off levels that provided at least 80% sensitivity were 24 for the Montreal Cognitive Assessment, 29 for the Mini-Mental State Examination and 87 for the Addenbrooke's Cognitive Evaluation-R. However, specificity levels were below 80% at these cut-off levels. CONCLUSIONS: We conclude that Level I assessment alone using screening batteries is not sufficiently sensitive/specific to detect PD-MCI.

SYNE1 related cerebellar ataxia presents with variable phenotypes in a consanguineous family from Turkey.

SYNE1 related autosomal recessive cerebellar ataxia type 1 (ARCA1) is a late-onset cerebellar ataxia with slow progression originally demonstrated in French-Canadian populations of Quebec, Canada. Nevertheless, recent studies on SYNE1 ataxia have conveyed the condition from a geographically limited pure cerebellar recessive ataxia to a complex multisystem phenotype that is relatively common on the global scale. To determine the underlying genetic cause of the ataxia phenotype in a consanguineous family from Turkey presenting with very slow progressive cerebellar symptoms including dysarthria, dysmetria, and gait ataxia, we performed SNP-based linkage analysis in the family along with whole exome sequencing (WES) in two affected siblings. We identified a homozygous variant in SYNE1 (NM_033071.3: c.13086delC; p.His4362GlnfsX2) in all four affected siblings. This variant presented herein has originally been associated with only pure ataxia in a single case. We thus present segregation and phenotypic manifestations of this variant in four affected family members and further extend the pure ataxia phenotype with upper motor neuron involvement and peripheral neuropathy. Our findings in turn established a precise molecular diagnosis in this family, demonstrating the use of WES combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.

EFNS-ENS Guidelines on the diagnosis and management of disorders associated with dementia.

BACKGROUND AND OBJECTIVES: The last version of the EFNS dementia guidelines is from 2007. In 2010, the revised guidelines for Alzheimer's disease (AD) were published. The current guidelines involve the revision of the dementia syndromes outside of AD, notably vascular cognitive impairment, frontotemporal lobar degeneration, dementia with Lewy bodies, corticobasal syndrome, progressive supranuclear palsy, Parkinson's disease dementia, Huntington's disease, prion diseases, normal-pressure hydrocephalus, limbic encephalitis and other toxic and metabolic disorders. The aim is to present a peer-reviewed evidence-based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists and other specialist physicians responsible for the care of patients with dementing disorders. It represents a statement of minimum desirable standards for practice guidance. METHODS: The task force working group reviewed evidence from original research articles, meta-analyses and systematic reviews, published by June 2011. The evidence was classified (I, II, III, IV) and consensus recommendations graded (A, B, or C) according to the EFNS guidance. Where there was a lack of evidence, but clear consensus, good practice points were provided. RESULTS AND CONCLUSIONS: New recommendations and good practice points are made for clinical diagnosis, blood tests, neuropsychology, neuroimaging, electroencephalography, cerebrospinal fluid (CSF) analysis, genetic testing, disclosure of diagnosis, treatment of behavioural and psychological symptoms in dementia, legal issues, counselling and support for caregivers. All recommendations were revised as compared with the previous EFNS guidelines. The specialist neurologist together with primary care physicians play an important role in the assessment, interpretation and treatment of symptoms, disability and needs of dementia patients.

Genetic bases and phenotypes of autosomal recessive Parkinson disease in a Turkish population.

BACKGROUND AND PURPOSE: To evaluate the phenotype and the frequencies of mutations in PRKN, DJ1 and PINK1 genes in patients with Parkinson disease (PD) in Turkey. METHODS: Eighty-six patients from 77 PD families participated in the study. Seventy-four families were originating from Turkey, two families from Greece and one family from Bulgaria. All patients underwent detailed neurological examination. PRKN, PINK1 and DJ1 genes were sequenced, and dosage analysis was performed by multiplex ligation-dependent probe amplification. RESULTS: Sixteen patients with PD were found to carry homozygous (n = 14) or compound heterozygous (n = 2) PRKN mutations. We identified exon rearrangements, three point mutations and one new point mutation in exon 2 (p.K27del). In two families, two new PINK1 point mutations (L31X and P416L) were identified. No pathogenic mutations were found in DJ1 gene. Clinical phenotypes of PRKN patients were comparable to previously described features, but only in four of 13 families, the pedigree structure was clearly consistent with an autosomal recessive (AR) mode of inheritance in comparison with nine families where also different pattern of transmission could have been possible. CONCLUSIONS: Our data suggest that the PRKN gene mutation is the most frequent form of ARPD in Turkey. The proportion of mutations with regard to the age of onset in our population is in the range of those previously described, but our pedigrees are characterized by high rate of consanguinity, which might explain the high proportion of families with homozygous mutations and of patients in more than one generation. Pathogenic DJ1 mutations do not seem to play a major role in Turkey.

The combinations of TNFalpha-308 and IL-6 -174 or IL-10 -1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer's disease.

OBJECTIVE: Single nucleotide polymorphisms in the regulatory regions of the cytokine genes for tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL-10 have been suggested to influence the risk of Alzheimer's disease (AD) with conflicting results. AIM: To investigate the TNFalpha-308, IL-6 -174 and IL-10 -1082 gene polymorphisms as susceptibility factors for AD. METHODS: We analyzed genotype and allele distributions of these polymorphisms in 101 sporadic AD patients and 138 healthy controls. RESULTS: Heterozygotes (AG) or combined genotype (AG+AA) for IL-10 -1082 were associated with approximately two-fold increase in the risk of AD. Carriers of A alleles of both TNFalpha-308 and IL-10 -1082 had 6.5 times higher risk for AD in comparison with non-carriers. Concomitant presence of both mutant TNFalpha-308 A and IL-6 -174 C alleles raised three-fold the AD risk, whereas there was no notable risk for AD afflicted by IL-6 -174 polymorphism alone. CONCLUSION: Our results suggest that TNFalpha and IL-10 promoter polymorphism might be a risk factor for AD. The combined effects of TNFalpha-308, IL-6 -174 and IL-10 -1082 variant alleles may be more decisive to induce functional differences and modify the risk for AD.

The prevalence of dementia in an urban Turkish population.

A cross-sectional, population-based, 2-stage prevalence study was conducted in a sample of 1019 community-dwelling persons over the age of 70 years living in Istanbul. In the first phase, participants were screened with the Mini-Mental State Examination for evidence of cognitive impairment. In the second phase, 79% of those who screened positive (n = 322) and 9% of screen-negatives (n = 63) underwent a standardized diagnostic workup. Diagnosis of dementia and Alzheimer's disease (AD) was made according to established criteria. Ninety-three cases of dementia were identified, 58 of whom were diagnosed with probable AD. Based on these numbers, the prevalence rates of probable AD and dementia were calculated to be 11.0% (95% CI, 7.0% to 15.0%) and 20.0% (95% CI, 14.0% to 26.0%), respectively, in this population. Prevalence rates of dementia and AD in Istanbul, Turkey, are comparable with those seen in the Western world.

Cortical excitability in Duchenne muscular dystrophy.

OBJECTIVE: To investigate the probable cortical excitability changes in DMD by electrophysiological means. METHODS: Sixteen cases with DMD, 10 age-matched control children (CC) and 10 healthy adult volunteers (AC) were studied with a transcranial magnetic stimulation (TMS) test battery composed of central conduction time, cortical silent period and paired TMS paradigm. RESULTS: There were no significant differences between DMD and CC groups except for lower amplitude motor responses in DMD cases. These two groups showed a similar pattern of excitability with less short interval intracortical inhibitions and shorter silent period durations as compared to the AC subjects. CONCLUSIONS: The electrophysiological tests performed in our DMD patients did not reveal abnormalities caused particularly by the disorder. SIGNIFICANCE: TMS excitability studies performed in DMD boys may not provide findings other than those related to the developmental age.

The Arg194Trp polymorphism in DNA repair gene XRCC1 and the risk for sporadic late-onset Alzheimer's disease.

Alzheimer's disease (AD) is defined pathologically by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. Evidence indicates that increased DNA damage may contribute to neuronal loss in AD. Recently, it has been shown that in AD neurons have a reduced capacity for some types of DNA repair. Polymorphisms in DNA repair genes may be associated with differences in repair efficiency of DNA damage. Variants of several DNA repair genes, including the base excision repair gene XRCC1, have been described previously. We hypothesised that Arg194Trp polymorphism of XRCC1 gene may contribute to genetic susceptibility for AD. In order to test this hypothesis, we investigated Arg194Trp polymorphism at the XRCC1 gene in the DNA samples of 98 patients with AD and 95 healthy subjects. The frequency of the Trp allele was more pronounced among cases (11.2%) compared with controls (5.8%). On combining the homozygous and heterozygous variants of each codon, the variants seemed to be at twofold risk of AD, although the risk estimates were not statistically significant (OR=1.95, 95% CI 0.88-4.34, p=0.09). In addition, the 194Trp allele revealed a borderline significance (OR=2.05, 95% CI 0.96-4.37, p=0.056). According to our results, it may be speculated that the polymorphic variants of XRCC1 codon 194 have a role in the development of AD.

Inflammatory/demyelinating central nervous system involvement in familial Mediterranean fever (FMF): coincidence or association?

BACKGROUND AND OBJECTIVE: Familial Mediterranean fever (FMF) is an inherited inflammatory disease characterized by recurrent febrile polyserositis. Central nervous system (CNS) involvement in FMF is uncommon, but recently cases with multiple sclerosis (MS) and FMF have been reported. Here we assess patients with both FMF and MS, in order to clarify any relationship between FMF and MS, and to evaluate disease characteristics. PATIENTS AND METHODS: Our MS database between 1986-2005 was screened retrospectively, and patients with both FMF and inflammatory/demyelinating CNS disease were evaluated among a total of 2800 patients including definite MS (n = 2268) and other demyelinating disorders. RESULTS: There were 12 patients with FMF, who developed a CNS disorder with multifocal white matter lesions. Median age at onset of FMF was 7 years, and median age at neurological onset was 26.8 years. Nine patients (including two siblings) had definite MS according to clinical and MRI findings, whereas 3 patients had atypical features suggesting other demyelinating disorders. Disease severity varied among the patients between very mild to a fatal course. All 8 patients evaluated for oligoclonal IgG bands in CSF were positive. CONCLUSION: The rate of FMF among our patients with definite MS is almost 4 times the expected prevalence in Turkey. Our series including a sibling pair concordant for FMF and MS may suggest that similar genetic susceptibility and environmental factors might be responsible, although coincidence still remains a possibility. A prospective study on a larger sample seems to be justified.

Neuromuscular consequences of prolonged hunger strike: an electrophysiological study.

OBJECTIVES: The purpose of this study was to determine the electrophysiological consequences of neuromuscular and central nervous system involvement in a group of patients presented with the neurological complications of a long-term hunger strike (HS). METHODS: Motor and sensory nerve conduction (NCV), F wave, somatosensory evoked potential (SEP) and motor evoked potential (MEP) studies were performed in 12 male and 3 female patients (mean age: 29.4) following HS. RESULTS: All patients whose weight loss was 11-31 (mean: 22.8) kg after 69-day HS, had neurological findings consistent with Wernicke's encephalopathy or Wernicke-Korsakoff syndrome. Abnormally prolonged latency and/or low amplitude sensory nerve action potentials were found in 7 patients. The amplitudes of compound muscle action potentials were significantly reduced in ulnar, median and tibial motor NCV studies as compared to the controls. F waves elicited by median nerve stimulation at wrist and muscle responses evoked by cervical and lumbar magnetic stimulation had significantly prolonged latencies. MEPs recorded from the lower extremities showed a slight prolongation in central conduction times. The cortical response latencies were prolonged in tibial SEPs. CONCLUSIONS: The most prominent finding in this patient group was the low amplitude of CMAPs elicited in motor NCV studies which was concluded to be resulted from the reversible muscular changes. The other electrophysiological findings suggested that peripheral nerves and long central nervous system pathways were also mildly involved.

Paraneoplastic limbic encephalitis with immature ovarian teratoma--a case report.

Paraneoplastic limbic encephalitis (PLE) is a remote, nonmetastatic complication of carcinoma. Neuropsychiatric symptoms usually predate the diagnosis of cancer by 3 months to 6 years and very rarely the symptoms develop after the diagnosis of malignancy. We report the first case of limbic encephalitis associated with an immature ovarian teratoma. Within the month following the diagnosis of the tumor with pathologic stage Ia, somewhat acutely she developed neuropsychiatric symptoms that was exclusively a limbic disorder with impairments in almost every realm of limbic function. This case may show us that it is important to recognize the neuropsychiatric symptoms of PLE as the first manifestation of a very small malignant ovarian tumor and to aggressively try to identify the underlying cancer.

Magnetic nerve root stimulation in two types of brachial plexus injury: segmental demyelination and axonal degeneration.

Magnetic cervical nerve root stimulation was performed in 9 patients with plexopathies secondary to suspension (SP) and in 12 cases with neurogenic thoracic outlet syndrome (NTOS). The findings were compared with those of the previously reported case groups: n-hexane polyneuropathy (HPNP), inflammatory demyelinating polyneuropathy (IDP), and motor neuron disease (MND). Muscle responses elicited by magnetic stimulation had very high rates of amplitude and area loss in the neck-axilla segments of the 6 SP patients. This, along with the other electrophysiological findings, suggested the presence of segmentally demyelinating plexus lesions. In NTOS patients, magnetic stimulation findings were not significantly different from those of the controls. Neck-axilla segment amplitude and are reduction rates in SP and IDP patients were significantly higher than those found in NTOS, HPNP, and MND groups, implying that magnetic nerve root stimulation may have a role in the demonstration of segmentally demyelinating lesions involving proximal nerve segments.

Seven-year follow-up of neurologic involvement in Behçet syndrome.

OBJECTIVE: To determine the long-term prognosis of neurologic involvement in Behçet syndrome. DESIGN: Forty-six patients with Behçet syndrome, who had been the subjects of a previous report with short-term follow-up, were reexamined 7 years later; 42 of them could be reexamined neurologically. Neuropsychological testing, magnetic resonance imaging, electromyography, and evoked potential studies were performed when available. RESULTS: Of the 27 patients who had had headaches without any neurologic symptoms or signs previously, 2 had developed an acute neurologic attack. In addition, 7 patients in this group showed minor abnormalities on neurologic examination and/or other laboratory investigations, without history of any attacks. Among the previous neuro-Behçet group (n = 15), as defined by the presence of neurologic signs or symptoms, other than headache, 7 had a stationary course, while 8 had been progressive. Three of the latter group had died. Patients with progressive course had had abnormal cerebrospinal fluid findings at the time of the previous report, whereas patients with a stationary course had not. CONCLUSIONS: Silent neurologic involvement may occur in Behçet syndrome. Patients should undergo periodic neurologic evaluation. The long-term prognosis in neuro-Behçet syndrome does not seem to be as favorable as we observed in short-term follow-up. Cerebrospinal fluid findings may predict prognosis.

Neuropsychological patterns and language deficits in 20 consecutive cases of autopsy-confirmed Alzheimer's disease.

A retrospective chart review of clinical symptoms was done for 20 consecutive patients in whom postmortem examination had revealed senile plaques and neurofibrillary tangles in a distribution consistent with Alzheimer's disease. All patients had met clinical diagnostic criteria for probable Alzheimer's disease. On initial examination, 1 to 14 years beyond putative onset of the dementia, all patients displayed at least some memory impairment. In 16 patients, disturbances of attention or recent memory were among the most salient features. In two patients, language disturbances, and in two others, visuospatial deficits, were more prominent than difficulties with memory and attention. On initial examination, 17 of the 20 patients displayed word-finding difficulties, characteristically in the context of a fluent, anomic aphasia. All of the 12 reexamined patients demonstrated progressive, although variable, deterioration. In general, the initial salient deficit remained salient during much of the disease course. Language comprehension was spared in the earlier stages but eventually deteriorated. Severe deficits emerged in all major cognitive domains as the disease reached the terminal stages. Nonfluent aphasias (eg, Broca's aphasia) were not observed even in the advanced stages of the disease.