Neurological Evaluation of Patients with Newly Diagnosed Coeliac Disease Presenting to Gastroenterologists: A 7-Year Follow-Up Study.

We have previously shown that 67% of patients with newly diagnosed coeliac disease (CD) presenting to gastroenterologists have evidence of neurological dysfunction. This manifested with headache and loss of co-ordination. Furthermore 60% of these patients had abnormal brain imaging. In this follow-up study, we re-examined and re-scanned 30 patients from the original cohort of 100, seven years later. There was significant reduction in the prevalence of headaches (47% to 20%) but an increase in the prevalence of incoordination (27% to 47%). Although those patients with coordination problems at baseline reported improvement on the gluten free diet (GFD), there were 7 patients reporting incoordination not present at baseline. All 7 patients had positive serology for one or more gluten-sensitivity related antibodies at follow-up. In total, 50% of the whole follow-up cohort were positive for one or more gluten-related antibodies. A comparison between the baseline and follow-up brain imaging showed a greater rate of cerebellar grey matter atrophy in the antibody positive group compared to the antibody negative group. Patients with CD who do not adhere to a strict GFD and are serological positive are at risk of developing ataxia, and have a significantly higher rate of cerebellar atrophy when compared to patients with negative serology. This highlights the importance of regular review and close monitoring.

Geospatial association of endemicity of ataxic polyneuropathy and highly cyanogenic cassava cultivars.

BACKGROUND: Exposure to cyanide from cassava foods is present in communities where ataxic polyneuropathy is endemic. Ataxic polyneuropathy is endemic in coastal parts of southwest and southeast Nigeria, and coastal Newala, south India, but it has been reported in epidemic or endemic forms from Africa, Asia, or Caribbean. This study was done to determine if cyanogenicity of cassava cultivars is higher in lowland than highland areas, and if areas of endemicity of ataxic polyneuropathy colocalize with areas of highest cyanogenicity of cassava. METHODS: Roots of cassava cultivars were collected from 150 farmers in 32 of 37 administrative areas in Nigeria. Global positioning system was used to determine the location of the roots. Roots were assayed for concentrations of cyanogens. Thin Plate Spline regression was used to produce the contour map of cyanogenicity of the study area. Contour maps of altitude of the endemic areas were produced. Relationship of cyanogenicity of cassava cultivars and altitude, and of locations of areas of high cyanogenicity and areas of endemicity were determined. RESULTS: Geometrical mean (95% CI) cyanogen concentration was 182 (142-233) mg HCN eq/kg dry wt for cassava cultivars in areas ≤ 25 m above sea level, but 54 (43-66) mg HCN eq/kg dry wt for areas > 375 m. Non-spatial linear regression of altitude on logarithm transformed concentrations of cyanogens showed highly significant association, (p < 0.0001). Contour map of concentrations of cyanogens in cassava cultivars in Nigeria showed four areas with average concentrations of cassava cyanogens > 250 mg HCN eq/kg dry wt, and one area of moderately high cyanogen concentration > 150 mg HCN eq/kg dry wt. The endemic areas colocalized with areas of highest cassava cyanogenicity in lowland areas close to the Atlantic Ocean. CONCLUSION: This study shows strong geospatial association of areas of endemicity of ataxic polyneuropathy and areas of highest cyanogenicity of cassava cultivars. Finding of higher cyanogenicity of cassava in lowland than highland areas indicate strong influence of altitude on expression of cyanogens in cassava cultivars.

Relationship between fatigue and gait abnormality in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type.

Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It has recently been shown that muscle weakness occurs frequently in EDS, and that fatigue is a common and clinically important symptom. The aim of this study was to investigate the relationship between fatigue severity and the gait pattern using 3D Gait Analysis (GA). Eleven individuals with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility type (JHS/EDS-HT) were investigated using muscle strength measured with standardised questionnaire measuring fatigue (Fatigue Severity Scale, FSS) and quantitative 3D GA. Our data showed that FSS value well correlated with the peak of vertical component of ground reaction force (r=-0.66, p<0.05). The negative correlation gives evidence that the higher the fatigue is the more reduced force is during gait. Our results showed that the ground reaction force has been applied as a functional evaluation score for detecting pathology in gait of JHS/EDS-HT participants and the found correlation between vertical force and fatigue demonstrated that muscle fatigue may be associated with a loss of proprioceptive acuity in lower limb muscles.

[Walking and ageing]. / Marche et vieillissement.

As we get older, our gait changes insidiously with a tendency for us to walk more slowly, to take shorter strides and to increase the time when both feet are on the ground. Four major factors are most often found interlinked in walking problems in the elderly. Being more aware of them enables healthcare teams to adapt the care provided to elderly patients.

[Anti-MAG paraproteinemic demyelinating polyneuropathy: a clinical, biological, electrophysiological and anatomopathological descriptive study of a 13-patients' cohort]. / Les polyneuropathies avec IgM monoclonale anti-MAG : étude descriptive clinique, biologique, électrophysiologique et anatomopathologique d'une cohorte de 13 patients.

INTRODUCTION: Polyneuropathies associated with IgM paraproteinemia and anti-myelin associated glycoprotein (MAG) antibodies (MAG-PN) have to be differentiated from chronic inflammatory demyelinating polyneuropathies. METHODS: In a retrospective study, we have analyzed clinical, electrophysiological, biological and pathological data from MAG-PN patients. RESULTS: Seven male and six female patients were followed in the department for a mean 2 years (0.5-6.5 years). Mean age at diagnosis was 61 years (44.5-85.5 years). Patients had symmetrical bilateral paresthesia (11/13) and hypoesthesia (11/13) prominent in the lower limbs. Nine patients developed gait ataxia and four patients had moderate distal weakness in the lower limbs. Mean Overall Neuropathy Limitation Scale was 2.3 (0-5). Nerve conduction study showed demyelinating features though delayed distal motor latency on median (206 % of normal value) and ulnar nerves (150% of normal value). Seven out of thirteen patients had at least two nerves with terminal latency index below 0.25. IgM paraproteinemia was of undetermined significance in ten cases and three patients had non-Hodgkin lymphoma. IgM deposits and widening of the peripheral myelin were observed in 5/7 sural nerve biopsies. Anti-MAG antibodies were detected in the sera of all patients using enzyme-linked immunosorbent assay and in 8/12 patients using western blot analysis. CONCLUSIONS: MAG-PN have distinctive clinical, electrophysiological and pathological features. It is a chronic, slowly progressive, predominantly sensory and ataxic neuropathy. Disability is usually moderate. Electrophysiological study shows distal demyelinating process and is highly suggestive of MAG-PN in more than one half of our patients. Several techniques may detect anti-MAG antibodies, they have to be associated to improve sensitivity and specificity of the test.

Disease suspected to be caused by Ross River virus infection of horses.

Ross River Virus (RRV) was believed to be the cause of acute illness in four horses around the Bellarine peninsula in south-west Victoria, Australia. The horses presented with clinical signs including petechial haemorrhages, lymphadenopathy, distal limb swelling and reluctance to move. Fibrinogen was also elevated in three of the four horses. Whilst no virus was isolated, serological testing revealed elevated RRV IgM titres in all horses indicating acute infection. The outbreak occurred at a time when a known RRV vector, the mosquito Aedes camptorhynchus was recorded at very high levels in the region. This report is one of very few to attribute specific signs of disease to RRV in horses in conjunction with serological evidence of infection.

Measuring Friedreich ataxia: complementary features of examination and performance measures.

OBJECTIVE: To examine the potential validity of performance measures and examination-based scales in Friedreich ataxia (FA) by examining their correlation with disease characteristics. METHODS: The authors assessed the properties of a candidate clinical outcome measure, the Friedreich Ataxia Rating Scale (FARS), and simple performance measures (9-hole peg test, the timed 25-foot walk, PATA test, and low-contrast letter acuity) in 155 patients with FA from six institutions, and correlated the scores with disease duration, functional disability, activity of daily living scores, age, and shorter GAA repeat length to assess whether these measures capture the severity of neurologic dysfunction in FA. RESULTS: Scores for the FARS and performance measures correlated significantly with functional disability, activities of daily living scores, and disease duration, showing that these measures meet essential criteria for construct validity for measuring the progressive nature of FA. In addition, the FARS and transformed performance measures scores were predicted by age and shorter GAA repeat length in linear regression models accounting for sex and testing site. Correlations between performance measures were moderate in magnitude, suggesting that each test captures separate yet related dimensions of neurologic function in FA and that a composite measure might better predict disease status. Composite measures created using cohort means and standard deviations predicted disease status better than or equal to single performance measures or examination-based measures. CONCLUSIONS: The Friedreich Ataxia Rating Scale, performance measures, and performance measure composites provide valid assessments of disease progression in Friedreich ataxia.

Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin.

Mutations in the catalytic subunit of the mitochondrial DNA polymerase gamma (POLG) have been found to be an important cause of neurological disease. Recently, we and collaborators reported a new neurodegenerative disorder with autosomal recessive ataxia in four patients homozygous for two amino acid changes in POLG: W748S in cis with E1143G. Here, we studied the frequency of this allele and found it to be among the most common genetic causes of inherited ataxia in Finland. We identified 27 patients with mitochondrial recessive ataxia syndrome (MIRAS) from 15 Finnish families, with a carrier frequency in the general population of 1 : 125. Since the mutation pair W748S+E1143G has also been described in European patients, we examined the haplotypes of 13 non-Finnish, European patients with the W748S mutation. Haplotype analysis revealed that all the chromosomes carrying these two changes, in patients from Finland, Norway, the United Kingdom, and Belgium, originate from a common ancient founder. In Finland and Norway, long, common, northern haplotypes, outside the core haplotype, could be identified. Despite having identical homozygous mutations, the Finnish patients with this adult- or juvenile-onset disease had surprisingly heterogeneous phenotypes, albeit with a characteristic set of features, including ataxia, peripheral neuropathy, dysarthria, mild cognitive impairment, involuntary movements, psychiatric symptoms, and epileptic seizures. The high carrier frequency in Finland, the high number of patients in Norway, and the ancient European founder chromosome indicate that this newly identified ataxia should be considered in the first-line differential diagnosis of progressive ataxia syndromes.

Rigidity and bradykinesia reduce interlimb coordination in Parkinsonian gait.

OBJECTIVE: To assess the influence of rigidity and bradykinesia and the extent of dopaminergic degeneration on interlimb coordination during walking in early, drug-naive patients with Parkinsons disease (PD). DESIGN: The interlimb coordination was examined during a systematic manipulation of walking speed on a treadmill. The phase relations between arm and leg movements were related to the clinical measures of rigidity and bradykinesia as well as to the extent of dopaminergic degeneration. SETTING: Movement disorders outpatient clinic (including motion analysis laboratory) and a nuclear medicine department of a university hospital. PARTICIPANTS: Twenty-nine early and drug-naive PD patients. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The interlimb coordination during walking was evaluated by studying the (continuous) relative phase relations between movements of arms and legs. The clinical assessment of rigidity and bradykinesia was performed by using the Unified Parkinson Disease Rating Scale. The dopaminergic degeneration was expressed as striatal 2beta-carboxymethoxy-3beta-(4-iodophenyl) tropane (beta-CIT) single-photon emission computed tomography (SPECT) binding. RESULTS: The mean relative phase between arm and leg movements increased significantly with walking speed in all patients. Significant correlations were found between the rigidity and bradykinesia and the coordination measures ( P

Predictors of outcome in patients with normal-pressure hydrocephalus.

Despite knowledge emerging over the last 40 years, the postoperative results after shunt implantation in patients diagnosed with normal-pressure hydrocephalus (NPH) have not improved significantly over the last decade. For that reason predictors have to be identified in order to preoperatively predict outcome. From 1982 to 2000 we prospectively studied 200 patients diagnosed with NPH. From the patients, who were surgically treated by a shunt implantation we reexamined 155 (78%) postoperatively a mean time interval of 7 months. The NPH was graded according to the results of the intrathecal infusion test in an early stage NPH (without brain atrophy) and late stage NPH (with brain atrophy). In our study, we focussed attention on the possible predictors: patients age, length of disease, clinical signs (gait ataxia, dementia and bladder incontinence), aetiology idiopathic/secondary as well as implanted valve type and the value of resistance to cerebrospinal fluid outflow. To measure the outcome we used the NPH recovery rate and as the statistical test the chi(2) according to Pearson. In 80 patients with an early stage NPH (without cerebral atrophy), a short course of disease (<1 year), a slight degree of dementia and an implanted Miethke-Dual-Switch valve were significant predictors for a positive postoperative outcome. The outflow resistance measured in the intrathecal infusion test showed only a minimal relevance to outcome. Those 75 patients with a late state NPH (with cerebral atrophy) had a better outcome when dementia was not present, the outflow resistance was above 20mm Hg/min/ml, the CSF tap-test was positive and a Miethke-Dual-Switch valve was implanted.

Neurodevelopmental outcome of infants supported with extracorporeal membrane oxygenation after cardiac surgery.

OBJECTIVES: To evaluate the long-term neurodevelopmental outcome of infants who underwent cardiac surgery and required extracorporeal membrane oxygenation (ECMO) support, and to examine variables that predict death or disability in these patients. METHODS: We studied all infants who had congenital heart disease and were supported postoperatively with ECMO from 1990 to 2001 at our institution (n = 53). Medical records were reviewed retrospectively to obtain clinical variables. Neurologic and age-appropriate developmental examinations occurred at ages 1, 1.5, 2.5, and 4.5 years. Median age at follow-up was 55 months (9-101). Cognitive outcome was defined as suspect when scores were between 1 and 2 SD below the mean for age and abnormal when scores were >2 SD below mean for age. Neuromotor outcome was defined as suspect when the patient manifested clumsiness, tremor, or mild tone and reflex changes without functional limitations, and abnormal when there were functional limitations. RESULTS: In-hospital survival was 17 (32%) of 53. Of survivors, 14 (88%) of 16 are living and 1 patient was lost to follow-up. Of the 53 patients, 7 survived completely intact (13%). Seven (50%) of 14 patients had a normal cognitive outcome, 3 (21%) had a suspect cognitive outcome, and 4 (29%) were abnormal. Ten (72%) of 14 patients had a normal neuromotor outcome, 1 (7%) patient had a suspect neuromotor outcome, and 3 (21%) were abnormal. No survivor with an aortic cross-clamp time >40 minutes had a normal cognitive outcome. Nonsurvivors were more likely than survivors to have had cardiac arrest as an indication for ECMO (31% vs 6%), to have had a longer aortic cross-clamp time (mean 73 minutes vs 32 minutes), and to have required continuous arteriovenous hemofiltration (78% vs 35%). The age and weight at cannulation, gender, cardiac diagnosis, interval from surgery to ECMO, cardiopulmonary bypass time, diagnosis of sepsis or mediastinitis, and duration of ECMO were not significantly associated with survival. CONCLUSIONS: Although mortality was 68% in infants who had congenital heart disease and were treated with ECMO postoperatively, of those who survive to hospital discharge, 75% have a normal neuromotor outcome and 50% have a normal cognitive outcome. These high rates of mortality and disability suggest that increased attention be paid to neuroprotection in these complex disorders.

Isolation of Ross River virus from mosquitoes and from horses with signs of musculo-skeletal disease.

OBJECTIVE: To report clinical and clinicopathological findings in horses naturally infected with Ross River virus (RRV) and identify likely mosquito arbovirus vector species. PROCEDURES: Veterinarians submitted serum samples from 750 horses because they suspected Ross River virus (RRV) infection. The samples were tested for the presence of IgM and IgG antibody to RRV and for the presence of virus. Mosquitoes were trapped, differentiated to species level and tested for the presence of RRV by virus isolation. RESULTS: RRV was isolated from six species of mosquitoes (Ochlerotatus camptorhyncus, Culex globocoxitus, Cx. australicus, Cx. annulirostris, Cx. quinquefasciatus, Anopheles annulipes) and from 13 horses with clinical signs of musculo-skeletal disease. Antibody to RRV was detected in 420 of the 750 serum samples; 307 contained IgG only; 76 contained both IgM and IgG and 37 contained only IgM antibody to RRV. Virus was isolated from horses with IgM antibody only. CONCLUSIONS: RRV can be isolated from infected horses during the short time period when there is an overlap of clinical signs, positive IgM serology and viraemia. Early spring infections of horses may occur if RRV infected mosquito vectors are present. RRV has not been shown to cause clinical disease in horses. This is the first report of isolation of RRV from Oc. camptorhyncus in the Murray region and indicates a potential for infection of humans and animals in autumn as well as in spring.

Clinical signs of cerebellar dysfunction in schizophrenia, alcoholism, and their comorbidity.

Abnormalities of cerebellar structure and function, long recognized as a hallmark of chronic alcohol abuse, have also occasionally been noted in patients with schizophrenia. We used a four-point rating scale to assess clinical signs of cerebellar dysfunction in men meeting DSM-IV criteria for schizophrenia (N=34) and alcohol dependence (N=15) as well as normal control subjects (N=28). Compared to controls, alcoholics had impaired ratings of gait ataxia and instability of stance with eyes closed, and schizophrenics had impaired ratings of stance with eyes closed. The incidence of dysdiadochokinesia was greater in schizophrenics, but not alcoholics, than controls. The incidence of gait and stance abnormalities was higher in both patient groups relative to controls: within the schizophrenic group, 50-70% of those with positive signs for gait or stance impairment were comorbid for alcoholism, while only 25% of those with positive signs for dysdiadochokinesia were comorbid for alcoholism. The presence of dysdiadochokinesia in the schizophrenic group suggests cerebellar dysfunction that is independent of the effects of alcohol. By contrast, clinical signs of cerebellar dysfunction of gait and stance in patients with schizophrenia may be secondary to the effects of alcohol on the cerebellum.

How common are complications of Parkinson's disease?

BACKGROUND: Parkinson's disease (PD) can be associated with a wide range of complications of advancing disease and treatment. However, it is unclear how often these occur in the overall population of patients with PD. OBJECTIVE: To assess the prevalence of disease and treatment complications and their clinical correlates in a community-based sample of 124 patients with PD. RESULTS: Average current age was 72 (SD 10.9) and mean disease duration 6 (SD 4.3) years. Falls with postural instability and other axial features were among the most common complications of advancing disease in this population (64 %). Motor fluctuations and dyskinesias affected approximately 30 and 20 % of the overall sample respectively, and changes in mental state such as dementia, depression and hallucinations each affected approximately one fifth of patients. Symptoms of autonomic nervous system dysfunction occurred in the great majority of patients, but were not associated with greater disease severity, disease duration or overall disability. CONCLUSION: In contrast to clinic-based samples, the most frequently occurring complications of PD in this community-based sample were axial features such as postural instability with falls. These factors should be more taken into account in the allocation of health care resources and the treatment of symptoms of patients with PD in the community.

Orthopaedic manifestations of familial dysautonomia. A review of one hundred and thirty-six patients.

BACKGROUND: Familial dysautonomia is a hereditary multisystemic disease primarily affecting people of Ashkenazi Jewish descent. Musculoskeletal problems are related to gait disorders, spinal deformities, foot deformities, fractures, and arthropathies. METHODS: The charts and radiographs of 136 patients who ranged in age from three months to forty-six years (mean, sixteen years) were reviewed. Sixty-four patients were available for follow-up examination. RESULTS: Spinal deformity was the most common orthopaedic problem and was diagnosed in seventy-eight patients starting at the age of four years, with a prevalence of 86 percent (forty-eight of fifty-six) by the age of fifteen years. Forty-one (53 percent) of the seventy-eight patients had scoliosis only, thirty-four (44 percent) had kyphoscoliosis, and three (4 percent) had kyphosis only. Bracing was accompanied by emotional, pulmonary, and skin problems, leading to a high rate of noncompliance and progression of the curve. Twenty-four patients had an operation at a mean age of thirteen years (range, five to eighteen years): twenty patients had posterior spinal arthrodesis, and four had combined anterior and posterior arthrodesis. Fifteen patients had a total of nineteen complications, of which seven were systemic and twelve were related to the spinal fixation. Eight patients had revision surgery. At the time of the surgery, scoliosis was corrected from a mean of 55 degrees to a mean of 35 degrees and kyphosis was corrected from a mean of 69 degrees to a mean of 61 degrees. After a mean duration of follow-up of sixty-five months, scoliosis measured 49 degrees (range, 18 to 62 degrees) and kyphosis measured 67 degrees (range, 30 to 115 degrees). Postoperative progression of the deformity was caused by failure of the instrumentation or progression in unfused segments. Walking was delayed in 72 percent (ninety-four) of the 130 patients who were of walking age. All sixty-four of the patients who were examined had an ataxic gait. Foot deformities were found in sixteen patients, six of whom were treated surgically. Two patients had Charcot joints. Fifty-five patients sustained at least one fracture before skeletal maturity, with a mean of 1.5 fractures per patient. All but one of the fractures was treated nonoperatively, and fracture-healing was often accompanied by profuse callus formation. CONCLUSIONS: Spinal deformity is common in patients with familial dysautonomia. Bracing is of questionable benefit, and surgical intervention should be considered once curve progression is well documented. Arthrodesis should be extended as far proximally as possible to prevent junctional kyphosis. Swelling and warmth in a limb should raise suspicion of an undiagnosed fracture.

[Distribution of dominant hereditary ataxias and Friedreich's ataxia in the Spanish population]. / Distribución de ataxias hereditarias dominantes y ataxia de Friedreich en la población española.

BACKGROUND: To establish the distribution of the different forms of dominant ataxias and Friedreich ataxia in Spanish population. PATIENTS AND METHODS: We have performed a molecular study in 121 patients presenting ataxia as the first sign of neurodegenerative disease. In these patients, we have performed a molecular study of SCA 1, SCA 2, SCA 3, SCA 6, SCA 7, SCA 8, DRPLA, alpha-TTP (tocopherol transfer protein) and Friedreich's ataxia genes. RESULTS: The study showed that the Friedreich ataxia is the most frequent form representing 34.4% of the total of the hereditary ataxias. One patient presented mutation in alpha-TTP gene. Among the dominant forms SCA 3 was the most frequent (27.3%) followed by SCA 7 (16%), SCA 6 (9%) and SCA 2 (4.5%). We have not found mutations in SCA 1 and DRPLA genes. Two of 60 apparently sporadic cases presented mutations in the SCA 6 and SCA 8. CONCLUSIONS: The genetic analysis is the principal method to distinguish the different clinic forms of ataxia. We have not found mutations in 41.2% of dominant forms and in 43.3% of recessive forms. These results suggest the existence of new candidates genes.

Persistence of tropical ataxic neuropathy in a Nigerian community.

OBJECTIVES: The term tropical ataxic neuropathy (TAN) is currently used to describe several neurological syndromes attributed to toxiconutritional causes. However, TAN was initially proposed to describe a specific neurological syndrome seen predominantly among the Ijebu speaking Yorubas in south western Nigeria. In this study, the prevalence of TAN was determined in Ososa, a semiurban community in south western Nigeria described as endemic for TAN in 1969, and its neurological features were compared with Strachan's syndrome, prisoners of war neuropathy, the epidemic neuropathy in Cuba, and konzo. METHODS: A census of Ososa was followed by door to door screening of all subjects aged 10 years and above with a newly designed screening instrument. Subjects who screened positive had a neurological examination, and the diagnosis of TAN was made if any two or more of bilateral optic atrophy, bilateral neurosensory deafness, sensory gait ataxia, or distal symmetric sensory polyneuropathy were present. RESULTS: A total of 4583 inhabitants were registered in the census. Of these, 3428 subjects aged 10 years and above were screened. The diagnosis of TAN was made in 206 of 323 subjects who screened positive for TAN. The prevalence of TAN was 6. 0%, 3.9% in males and 7.7% in females. The highest age specific prevalence was 24% in the 60-69 years age group in women. CONCLUSION: The occurrence of TAN in Ososa continues at a higher prevalence than was reported 30 years ago. Its neurological features and natural history do not resemble those described for Strachan syndrome, epidemic neuropathy in Cuba, or konzo. The increasing consumption of cassava foods linked to its causation makes TAN of public health importance in Nigeria, the most populous African country.