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Background Identifying the cause of non-traumatic coma in the emergency department is challenging. The clinical neurological examination is the most readily available tool to detect focal neurological deficits as indicators for cerebral causes of coma. Previously proposed clinical pathways have granted the interpretation of clinical findings a pivotal role in the diagnostic work-up. We aimed to identify the actual diagnostic reliability of the neurological examination with regard to identifying acute brain damage. Methods Eight hundred and fifty-three patients with coma of unknown etiology (CUE) were examined neurologically in the emergency department following a predefined routine. Coma-explaining pathologies were identified retrospectively and grouped into primary brain pathology with proof of acute brain damage and other causes without proof of acute structural pathology. Sensitivity, specificity and percentage of correct predictions of different examination protocols were calculated using contingency tables and binary logistic regression models. Results The full neurological examination was 74% sensitive and 60% specific to detect acute structural brain damage underlying CUE. Sensitivity and specificity were higher in non-sedated patients (87/61%) compared to sedated patients (64%/59%). A shortened four-item examination protocol focusing on pupils, gaze and pyramidal tract signs was only slightly less sensitive (67%) and more specific (65%). Conclusions Due to limited diagnostic reliability of the physical examination, the absence of focal neurological signs in acutely comatose patients should not defer from a complete work-up including brain imaging. In an emergency, a concise neurological examination should thus serve as one part of a multimodal diagnostic approach to CUE.

A 32-year-old woman presented in 2002 with a headache associated with numbness of her right arm, right side of her face and left leg. Examination was normal. Investigations revealed prolonged visual evoked responses (VER) on the right and a low vitamin B12 level. Cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI) of her brain and spine were normal. She was given a diagnosis of multiple sclerosis (MS) and commenced on vitamin B12 replacement. Three years later, her case was reviewed by the neurology service. She had experienced ongoing sensory disturbances, urinary dysfunction and episodic visual disturbances, consisting of blurred vision, particularly in her right eye, which would last for hours. She also experienced episodes of loss of strength of her right arm and a sensation of dragging her legs. Relevant past medical history included coeliac disease. Examination was normal. Investigations showed prolonged VERs, initially only on the right then bilateral. Somatosensory evoked potentials showed defective conduction in both lower limbs. MRI brain and spine were repeated and were normal. Oligoclonal bands in the CSF were normal. Autoimmune screen was negative. B12 and folate levels, thyroid function tests and syphilis serology were all negative. Tests for aquaporin-4 antibodies were performed twice using a cell based assay with aquaporin-4 M23 isoform and were positive. The titre was three out of four. Given her worsening VERs, with both being greater than 150 ms, her ongoing symptoms and positive aquaporin-4 antibodies, she was commenced on azathioprine. We believe that this patient’s symptoms are due to neuromyelitis optica (NMO). Therapy was initiated due to her prolonged VERs and our concerns regarding future functional visual deterioration. The patient was counseled with regard to the side effects of azathioprine but was very keen herself to commence therapy. Subjectively she feels better on treatment but there has been no change electrophysiologically. We believe that this patient is part of the evolving spectrum of NMO due to her clinical history, prolonged VERs, co-existent autoimmune disease and strongly positive aquaporin-4 antibodies. NMO is an inflammatory, demyelinating syndrome of the central nervous system with predominance of optic nerve and spinal cord involvement [1]. Aquaporin-4 antibodies were first described in 2004 [2]. The sensitivity of the aquaporin-4 antibody cell based assay ranges from 85 to 91% and the specificity is 100% [3, 4]. This patient’s symptoms were mild and her neurological examination was normal. Her symptoms were suggestive of mild transient optic neuritis and myelitis. Although her imaging has been normal thus far, it is possible that her disease may represent a milder phenotype of NMO and any radiological abnormalities present at the time of symptoms could reverse quickly leaving no appreciable abnormalities. The neurophysiological testing and the aquaporin-4 antibodies aided greatly in reaching a diagnosis in this patient and facilitating therapeutic decisions. Given the sensitivity P. H. McNamara (&) 32 Albert College Avenue, Glasnevin, Dublin 9, Ireland e-mail: pmcnamara2004@hotmail.com

Bilateral absence of cortical N20 responses of median nerve somatosensory evoked potentials (SEP) predicts poor neurological outcome in postanoxic coma after cardiopulmonary resuscitation (CPR). Although SEP is easy to perform and available in most hospitals, it is worthwhile to know how neurological signs are associated with SEP results. The aim of this study was to investigate whether specific clinical neurological signs are associated with either an absent or a present median nerve SEP in patients after CPR. Data from the previously published multicenter prospective cohort study PROPAC (prognosis in postanoxic coma, 2000–2003) were used. Neurological examination, consisting of Glasgow Coma Score (GCS) and brain stem reflexes, and SEP were performed 24, 48, and 72 h after CPR. Positive predictive values for predicting absent and present SEP, as well as diagnostic accuracy were calculated. Data of 407 patients were included. Of the 781 SEPs performed, N20 s were present in 401, bilaterally absent in 299, and 81 SEPs were technically undeterminable. The highest positive predictive values (0.63–0.91) for an absent SEP were found for absent pupillary light responses. The highest positive predictive values (0.71–0.83) for a present SEP were found for motor scores of withdrawal to painful stimuli or better. Multivariate analyses showed a fair diagnostic accuracy (0.78) for neurological examination in predicting an absent or present SEP at 48 or 72 h after CPR. This study shows that neurological examination cannot reliably predict absent or present cortical N20 responses in median nerve SEPs in patients after CPR.

Neuropsychiatric manifestations (NP) are common in systemic lupus erythematosus (SLE). However, the pathophysiological mechanisms are not completely understood. Neurofilament light protein (NfL) is part of the neuronal cytoskeleton. Increased NfL concentrations, reflecting neurodegeneration, is observed in cerebrospinal fluid (CSF) in several neurodegenerative and neuroinflammatory conditions. We aimed to explore if plasma NfL could serve as a biomarker for central nervous system (CNS) involvement in SLE. Sixty-seven patients with SLE underwent neurological examination; 52 underwent lumbar puncture, while 62 underwent cerebral magnetic resonance imaging (MRI). We measured selected auto-antibodies and other laboratory variables postulated to have roles in NP pathophysiology in the blood and/or CSF. We used SPM12 software for MRI voxel-based morphometry. Age-adjusted linear regression analyses revealed increased plasma NfL concentrations with increasing creatinine (β = 0.01, p

There is scarce data as to the association between physical activity and the volumes of subcortical brain regions in people with multiple sclerosis (PwMS). To compare the volumetric measures of subcortical brain structures in physically active and insufficiently active PwMS. This cross‐sectional study comprised 153 PwMS (39.3 ± 12.0 years, 68.0% female) who had undergone a complete neurological examination, computerized cognitive evaluation and brain MRI (using a high‐resolution scanner). MRI volumetric analysis was based on the FreeSurfer image analysis suite. Regions of interest included the hippocampus, amygdala, brain stem, basal ganglia, thalamus, accumbens nucleus, putamen, caudate and pallidum. Two MRI metrics, total volume (mm3) and estimated percentile of the subcortical region according to adjusted normative population, were calculated for each individual and brain region. Based on scores obtained from the Godin Leisure-Time Exercise Questionnaire, the cohort was subsequently divided into two groups, physically active (n = 77) and insufficiently active (n = 76). The left hippocampus estimated percentile point significantly differentiated between active and insufficiently active PwMS (48.5 (S.D. = 32.2) vs. 36.4 (S.D. = 29.8); p = 0.004), even after controlling for disability (p = 0.011) and cognition (p = 0.021). The right hippocampal estimated percentile point was also significantly different between groups (46.7 (S.D. = 30.6) vs. 34.6 (S.D. = 30.8); p = 0.004). Subcortical volume of the right hippocampus explained 19.4% of the variance between the groups (p = 0.008), even after controlling for disability (p = 0.013) and cognition (p = 0.020). Our results provide evidence that PwMS who regularly participate in leisure-time physical activities maintain their hippocampal volume, regardless of their disability and cognitive capabilities.

Background Positional manoeuvres are an important part of the neurological examination, particularly in patients with vertigo where the presence and characteristics of provoked nystagmus can help differentiate central from peripheral neurological disorders. Methods Case series of functional positional eye and eyelid movements. Results We report four patients with functional eye and eyelid movements provoked during positional manoeuvres. The range of abnormalities observed included positional convergence spasm, brief functional saccadic oscillations, and excessive positional blinking mimicking upbeat nystagmus. The functional movements described were present on a background of pre-existing peripheral or central nystagmus, or positional vertigo. Conclusion Functional positional eye and eyelid movements may co-exist with organic nystagmus that renders an accurate interpretation of the manoeuvre more challenging. A thorough understanding of the clinical features that differentiate these two categories of eye/eyelid movements makes the analysis easier, thus preventing misdiagnosis and avoiding unnecessary investigations.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a B-cell-mediated disease with autoimmunity towards the astrocyte water channel aquaporin-4 (AQP-4) in the central nervous system. Objective: To assess the long-term safety and efficacy in NMOSD patients receiving maintenance therapy with B-cell-depleting agent rituximab for more than 2 years. Method: NMOSD patients were included prospectively from 2014 to 2018 and received continuous cycles of rituximab infusions biannually. Incidence of adverse events (AE), serious AEs (SAE), and infusion-related AEs were evaluated through monthly phone calls and neurological examination every 4 months. Results: A total of 44 NMOSD patients were included, of those 30 were treatment naive (68%). The mean age was 37.2 years with 79.5% females. With overall observation period of 31.6 ± 7.3 months (24–48 months), tolerability was assessed as satisfactory in most cases. We observed infusion reactions (mostly mild) in 31.8% of patients and 31.8% never experienced any AEs after a mean 5.1 cycles of rituximab therapy. Rituximab was also beneficial in terms of improvement in relapse rate (from 0.26 ± 0.54 to 0, P = 0.003) and Expanded Disability Status Scale (from 4.1 ± 1.8 to 3.1 ± 1.8, P < 0.001). Stratification according to AQP4-IgG serostatus showed no difference between groups. Conclusion: Rituximab treatment is well tolerated, safe, and efficacious with a minor risk of mild infusion reactions for NMOSD patients.

The mechanism of action of fingolimod within the central nervous system and its efficacy in reducing/preventing both focal and diffuse grey matter (GM) damage in active multiple sclerosis (MS) are not completely understood. In this longitudinal, 2-year prospective, phase IV, single-blind study, 40 MS patients treated with fingolimod and 39 untreated age, gender, and disability-matched MS patients were enrolled. Each patient underwent a neurological examination every 6 months and a 3T MRI at the beginning of the treatment and after 24 months. The accumulation of new cortical lesions (CLs) and the progression of regional GM atrophy were compared between the two groups. At the end of the study (T24), the percentage of patients with new CLs (13.5 vs. 89%, p

To determine the optimal observation period (OBP) in adults with a clinical diagnosis of brain death (BD) using electroencephalography (EEG) or computerized tomography angiography (CTA). We conducted a retrospective observational analysis of adult patients with a diagnosis of BD from January 2000 to February 2017. The optimal OBP was defined as the minimum time interval from the first complete clinical neurological examination (CNE) that ensures that neither a second CNE nor any ancillary test (AT) performed after this period would fail to confirm BD. The study sample included 447 patients. In the supratentorial group, the first AT confirmed BD in 389 cases (98%), but in 8 (2%) cases the complementary test was incongruent. In this group, 8 of 245 patients in whom the first AT was carried out within the first 2 h after a complete CNE had a non-confirmatory test of BD versus none of 152 in whom the first AT was delayed more than 2 h (3.0% vs 0.0%; p = 0.026). In the infratentorial group, we found a higher probability of obtaining a first non-confirmatory AT of BD (34% vs 2%; p = 0.0001) and an OBP greater than 32.5 h was necessary to confirm a BD diagnosis. We found important differences in the confirmation of BD diagnosis between primary supratentorial and infratentorial lesion, and identified an optimal OBP of 2 h in patients with supratentorial lesions. By contrast, in primary posterior fossa/infratentorial lesions, the determination of an optimal OPB remains less accurate and hence more challenging.

International audience; The aim of this study is to investigate the frequency and the clinical correlations of pseudobulbar affect (PBA) in a population-based incident cohort of ALS patients. Incident ALS cases, diagnosed in 2011 and 2012, according to El Escorial criteria were enrolled from a prospective population-based registry in Apulia, Southern Italy. Neurological status was assessed using a standard neurological examination and the revised ALS Functional Rating Scale (ALSFRSr). The Center for Neurologic Study-Lability Scale (CNS-LS), a self-administered questionnaire, was used to evaluate the presence and severity of PBA. Total scores range from 7 to 35. A score ≥13 was used to identify the presence of PBA. One-hundred thirty-two sporadic incident ALS cases were enrolled. Median disease duration was 20 months (range 2-143), median onset-diagnosis interval (ODI) 12 months (range 2-131), median ALSFRSr at baseline 36/48 (range 2-47) and median ALSFRSr bulbar sub-score 10/12 (range 0-12). Neurological examination revealed presence of PBA in 34/132 patients (26%). Pathological CNS-LS score was found in 45/132 patients (34%). Median total CNS-LS score was 9/35 (range 7-29). The subgroup with pathological CNS-LS was characterized by a short disease duration from symptom onset, ODI, time to diffusion to a second region, time to generalization and ALSFRSr bulbar sub-score, bulbar onset, "definite" diagnostic category, bulbar upper motor-neuron involvement and presence of PBA at neurological examination. In population-based setting, one-third of ALS patients present PBA at diagnosis. The presence of PBA is associated with bulbar UMN involvement and markers of a more severe phenotype.

To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas’ scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 ± 5.0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological abnormality independently predicted transition to disability or death [HR (95 % CI) 1.53 (1.01–2.34)]. The hazard increased with increasing number of abnormalities. Among MRI lesions, only ARWMC of severe grade independently predicted disability or death [HR (95 % CI) 2.18 (1.37–3.48)]. In our cohort, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost-effective in identifying those at risk of functional decline.

The aim of this study was to determine the frequency, clinical and radiological features, and efficacy of clinical evaluation and perfusion-weighted imaging (PWI) for the prediction of final stroke in patients with DWI/MRI-negative posterior circulation stroke (PCS) presenting acute dizziness/vertigo. From our comprehensive prospective stroke registry of acute ischemic stroke during a 7-year period, we identified 1846 consecutive patients with PCS, 850 of whom presented with acute dizziness/vertigo. Of these 850 patients, initial DWI-MRI was negative in 35 (4.1%). In these 35 patients, dizziness/vertigo was acute prolonged in 31 and recurrent transient in 4. Focal neurological signs or profound imbalance were present in 16/35 or 18/34, respectively. Spontaneous nystagmus was absent in 21/35; the HINTS protocol (head impulse, nystagmus, and test-of-skew) was not applicable to them. In 12/26 patients, PWI was positive and the same time as DWI was negative. The usual site of lesion was the lateral medulla (n = 18). Twenty-nine patients (83%) had small strokes, while 19 (54%) had large vessel strokes. The sensitivity of systematic clinical evaluation adopting neurological examination, HINTS plus, and assessment of equilibrium was 83%, for prediction of final stroke and 100% when combined with PWI. An integrated approach using systematic neurological and neuro-otological examinations combined with PWI accurately diagnoses PCS presenting with acute dizziness/vertigo. Although most patients with acute vertigo and MRI-negative PCS have small brainstem strokes, about a half have large vessel stroke with greater risk of progression requiring prompt treatment.

Background Friedreich ataxia (FRDA) is an inherited movement disorder which manifests with progressive gait instability, sensory loss and cardiomyopathy. Peripheral neuropathy is an established feature of FRDA. At neuropathological examination, a depletion of large, myelinated axons is evident, but also unmyelinated fibers are affected which may result in a variety of sensory and autonomic signs and symptoms. Impaired temperature perception, vasomotor disturbances of lower extremities and a high prevalence of urinary symptoms have been documented in FRDA, but data from autonomic function testing in genetically confirmed cases are lacking. Methods Genetically confirmed FRDAs were recruited in an outpatient setting. In a screening visit, general and neurological examination, laboratory testing, ECG and echocardiography were performed. Autonomic functions were evaluated by means of systematic questionnaires (SCOPA-Aut, OHQ), skin sympathetic reflex and cardiovascular autonomic function testing (CAFT). For the latter, a comparison with matched healthy controls was performed. Results 20 patients were recruited and 13 underwent CAFT. Symptoms referred to multiple autonomic domains, particularly bladder function, thermoregulation and sweating were reported. SCOPA-Aut scores were significantly predicted by disease severity. At CAFT, FRDAs did not differ from controls except for increased heart rate at rest and during orthostatic challenge. Two patients had non-neurogenic orthostatic hypotension (14%). Skin sympathetic responses were pathologic in 3 out of 10 patients (of whom 2 aged > 50). Conclusions FRDA patients may experience several autonomic symptoms and overall their burden correlates with disease severity. Nonetheless, clinical testing shows no major involvement of sudomotor and cardiovascular autonomic function.

Tremor is the most frequent and disabling neurological side effect under Calcineurin inhibitor-induced immunosuppression, but no studies have defined its phenomenology, severity, distribution, the impact on quality of life, as well as of other neurological symptoms associated. 126 consecutive kidney-transplanted patients, under treatment with Cyclosporin A, Tacrolimus and non-Calcineurin inhibitors, within therapeutic range, were enrolled. Participants underwent a deep neurological examination by two blinded to the treatment raters, and a blood sampling to assess plasmatic immunosuppressant level and nephrological function tests. Tremor and cerebellar signs were scored according to the Fahn–Tolosa–Marin and the SARA scale. Parkinsonism was excluded applying the UPDRS (part III). Tremor was more common and severe in the Tacrolimus group, similar to impairment in ADL. Regardless of treatment, tremor involved both upper and lower limbs and was activated by action, but in about 50% of cases presented in action and rest condition. Plasmatic level of Tacrolimus was higher in patients with tremor than in those without, while cholesterol was significantly lower. Cerebellar and neuropathic signs were overall mild and were not significantly different across the three groups comparing patients with and without tremor. Non-Calcineurin inhibitors such as Sirolimus have the lowest propensity to induce tremor and with a milder severity, while Calcineurin inhibitors, especially Tacrolimus, the highest, and regardless of the formulation. Plasmatic concentration of Tacrolimus was higher in tremulous patients; further research needs to validate the role of cholesterol plasmatic concentration in predicting the occurrence of tremor in patients on Tacrolimus.

Focal epilepsy of unknown cause (FEUC) is an under-investigated topic despite its remarkable frequency. We aimed to report the long-term follow-up findings along with the drug-response, 5 year remission rates and diagnostic changes to give an insight about the heterogeneous characteristics of FEUC. Demographic, clinical, neurophysiological and imaging data of 196 patients diagnosed as FEUC according to ILAE criteria, with a minimum 5-year follow-up were evaluated in a tertiary epilepsy center. The drug resistance, 5 years of remission and relapse rates were investigated and the subgroups were compared statistically. The rate of drug resistance was 21.8% and status epilepticus (p

The objective of this study is to evaluate the nerve ultrasound characteristics in genetically distinct inherited neuropathies, the value of the modified ultrasound pattern sum score (mUPSS) to differentiate between the subtypes and the correlation of ultrasound with nerve conduction studies (NCS), disease duration and severity. All patients underwent a standardized neurological examination, ultrasound, and NCS. In addition, genetic testing was performed. Consequently, mUPSS was applied, which is a sum-score of cross-sectional areas (CSA) at predefined anatomical points in different nerves. 31 patients were included (10xCharcot-Marie-Tooth (CMT)1a, 3xCMT1b, 3xCMTX, 9xCMT2, 6xHNPP [Hereditary neuropathy with liability to pressure palsies]). Generalized, homogeneous nerve enlargement and significantly increased UPS scores emphasized the diagnosis of demyelinating neuropathy, particularly CMT1a and CMT1b. The amount of enlargement did not depend on disease duration, symptom severity, height and weight. In CMTX the nerves were enlarged, as well, however, only in the roots and lower limbs, most prominent in men. In CMT2 no significant enlargement was detectable. In HNPP the CSA values were increased at entrapped sites, and not elsewhere. However, a distinction from CMT1, which also showed enlarged CSA values at entrapment sites, was only possible by calculating the entrapment ratios and entrapment score. The mUPSS allowed distinction between CMT1a (increased UPS scores, entrapment ratios1.0) and HNPP (low UPS scores, entrapment ratios1.4), while CMT1b and CMTX showed intermediate UPS types and entrapment ratios1.0. Although based on few cases, ultrasound revealed consistent and homogeneous nerve alteration in certain inherited neuropathies. The modified UPSS is a quantitative tool, which may provide useful information for diagnosis, differentiation and follow-up evaluation in addition to NCS and molecular testing.

Walking limitation is a key component of dis- ability in patients with multiple sclerosis (MS), but the in- formation on daily walking activity and disability over time is limited. To determine, (1) the agreement between the standard measurements of MS-related disability (expanded disability status scale (EDSS), functional systems (FS) and ambulation index (AI)) obtained by conventional and re- mote evaluation using a multimedia platform; (2) the use- fulness of monitoring 6-min walk test (6MWT) and average daily walking activity (aDWA) to better characterize pa- tients disability. Twenty-five patients (EDSS score 1.0-6.5) were evaluated every 3 months for the first year, and aDWA repeated at year 2. Remote visits included the recording of a video with self-performed neurological examination and specific multimedia questionnaires. aDWA was measured by a triaxial accelerometer. All but two patients completed the study. Modest agreement between conventional and multimedia EDSS was found for EDSS B 4.0 (kap- pa = 0.2) and good for EDSS C 4.5 (kappa = 0.6). For the overall sample, pyramidal, cerebellar and brainstem FS showed the greatest agreement (kappa = 0.7). SR-AI showed a modest agreement for EDSS B 4.0 and good for EDSS C 4.5(kappa = 0.3and0.6,respectively).Therewas a strong correlation between conventional and 6MWT measured by accelerometer (r = 0.76). The aDWA corre- lated strongly with the EDSS (r =- 0.86) and a cut-off point of 3279.3 steps/day discriminated patients with ambulatory impairment. There was a significant decline in aDWA over 2 years in patients with ambulatory impairment that were not observed by standard measurements of dis- ability. MS clinical monitoring by telemedicine is feasible, but the observed lower agreement in less disabled patients emphasizes the need to optimize the assessment method- ology. Accelerometers capture changes that may indicate deterioration over time.

The aim of this study is to describe the frequency of isolated, subtle, neurological abnormalities (ISNAs) in a large population of neurologically and cognitively healthy subjects and to compare ISNAs to various types of MRI-detected cerebrovascular lesions and subcortical brain atrophy in different age classes. 907 subjects were selected from a large, prospective hospital-based study. At baseline neurological examination, 17 ISNAs were selected. Primitive reflexes were the most common ISNAs (35.8%), while dysphagia was the most rarely encountered (0.3%). Measures of small vessel disease, i.e., deep and subcortical white matter hyperintensity and lacunar infarcts as well as subcortical atrophy, were variously associated with ISNAs. In the adult group, the ISNAs were associated with hypertriglyceridemia, TIA, and subcortical lacunar infarcts, while in the elderly-old group they were associated with arterial hypertension, subcortical white matter hyperintensity, and subcortical atrophy. An increased risk of ISNAs was associated with lacunae and white matter hyperintensity in the parietal region. This study shows that white matter hyperintensity, lacunae, and subcortical atrophy are associated with an increased risk of ISNAs in cognitively and neurologically healthy aging subjects. ISNAs are not benign signs. Therefore, adults and elderly people presenting with ISNAs should have access to accurate history and diagnosis to prevent progression of small vessel disease and future neurological and cognitive disabilities.

Dear Sirs, Celiac disease (CD) may manifest only with neurological symptoms [5], even in advanced age [3]. No clear association has been reported to date between CD and Parkinson’s disease (PD). A 75-year-old man presented with a 1-year history of difficulty with walking, instability, and fatigability. Neurological examination showed facial hypomimia, bradykinesia, rigidity, and postural instability with a UPDRS/Part II score of 8 and a UPDRS/part III motor score of 19 (Table 1). The remaining neurological examination was unremarkable. The patient had never been treated with drugs acting on the central nervous system; in particular he had never received drugs causing parkinsonism such as neuroleptics. Brain MR revealed several nonspecific foci of hyperintensity in the frontal and parietal subcortical white matter but not in the basal ganglia. Few punctate calcifications were present in the globus pallidus bilaterally, a finding that is quite common in elderly subjects [6]. Singlephoton emission computed tomography (SPECT) after intravenous injection of 185 MBq of I-FP-CIT (DaTSCAN, G.E. Healthcare, UK) showed a pronounced decrease of radiotracer uptake in the left putamen and moderate decrease in the contralateral putamen (Fig. 1). Activity was clearly visible in the caudate nuclei of both hemispheres. Semi-quantitative analysis confirmed visual assessment of images: putamen-to-occipital cortex uptake ratios were lower than values obtained in healthy subjects, and the reduction was more pronounced on the left hemisphere. On the basis of clinical and SPECT data, a diagnosis of Parkinson’s disease was made. Laboratory studies revealed reduced serum folate level (2.8 ng/ml, n.v. 3–15) and hyperhomocysteinemia (23.4 lmol/l, n.v. 5–15), but vitamin B12 level was normal. The possibility of asymptomatic malabsortion due to a silent CD was explored. Serological screening revealed anti-gliadin antibodies, markedly elevated IgA (236 U/ml, n.v.\ 20) and IgG (86 U/ml; n.v. \ 20), anti-transglutaminase antibodies, and positive anti-endomysial antibodies. Duodenal histology was diagnostic of CD. The gastroenterologist prescribed a gluten-free diet. The patient came back to the neurological outpatient clinic only 3 months after the beginning of the gluten-free diet: during this period he had no pharmacological treatment for PD, but he reported an almost complete remission of symptoms. The improvement was confirmed by neurological evaluation, with a UPDRS/Part II score of 3 and a UPDRS/part III motor score of 8 (Table 1). Because of this improvement, we decided not to treat the patient at this stage. In order to define whether the gluten-free diet had modified striatum dopaminergic activity, we repeated the SPECT study 8 months after diet onset. SPECT confirmed the previous abnormalities and showed a further decrease in radiotracer uptake in the putamen bilaterally. Activity V. Di Lazzaro (&) F. Capone F. Ranieri Department of Neurosciences, Institute of Neurology, Campus Bio-Medico University, Via Alvaro del Portillo 200, 00128 Rome, Italy e-mail: v.dilazzaro@unicampus.it

The idiomuscular response to direct percussion is rarely tested nowadays because of its uncertain mechanism and significance. While performing neurological examination, we observed a brisk ankle dorsiflexion response on direct muscle percussion of m. tibialis anterior in patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP). In contrast, in patients with upper motor neuron lesions, an ankle inversion response was seen. In this article we describe our findings in patients with bilateral lower limb weakness. We assessed 73 consecutive patients with bilateral lower limb weakness. A strong dorsiflexion response to percussion of m. tibialis anterior was seen in 11 out of 14 patients with AIDP (sensitivity 78.6 %). None of the other patients showed a strong dorsiflexion response (specificity 100 %). An inversion response was seen in 11 out of 13 patients with UMN involvement (sensitivity 92.3 %). It was also noted in two of 46 patients without proven UMN involvement (specificity 96.7 %). The idiomuscular response to percussion of m. tibialis anterior can be useful in the assessment of patients with lower limb weakness of unclear cause.

The objective of this study was to analyze Charcot-Marie-Tooth disease type 1A (CMT1A) evolution. We conducted a 2-year longitudinal study in 14 CMT1A patients and 14 age- and sex-matched controls. In the patients, we performed neurological examination with hand-held dynamometry, electrophysiology, and lower-limb muscle MRI, both at baseline and 2 years later, while controls were examined at baseline only. Patients' ages ranged from 12 to 51 years. Outstanding manifestations on initial evaluation included pes cavus, areflexia, lower-limb weakness, and foot hypopallesthesia. In evaluating muscle power, good correlation was observed between manual testing and dynamometry. Compared to controls, Lunge, 10-Meter-Walking, and 9-Hole-Peg tests were impaired. Their CMT neuropathy score and functional disability scale showed that patients exhibited mild phenotype and at most slight walking difficulty. Electrophysiology revealed marked nerve conduction slowing and variable compound muscle action potential amplitude reduction. On lower-limb muscle MRI, there was distally accentuated fatty infiltration accompanied by edema in calf muscles. All these clinico-electrophysiological and imaging findings remained almost unaltered during monitoring. Using multivariate analysis, no significant predictors of progression associated to the disease were obtained. We conclude that in the 2-year period of study, CMT1A patients showed mild progression with good concordance between clinico-electrophysiological and imaging findings.

Dear Sirs, Patients with recurrent Guillain–Barre syndrome (RGBS) could show similar symptoms even with different types of preceding infections, thus genetic and immunological host factors are thought to partly determine the clinical phenotype irrespective of the preceding infection [1]. Although a previous study reported that the same antiganglioside antibodies were positive in sera obtained from the third and fourth recurrences of an RGBS patient with similar types of preceding infections [2], anti-ganglioside antibodies in RGBS cases with different types of preceding infections have not been reported. We treated a 37-year-old previously healthy man who developed weakness in the lower limbs 10 days after diarrhea development. On neurological examination, his limbs were moderately weak and deep tendon reflexes were abolished. Senses of temperature, pain, touch, position or vibration were not impaired. Nerve conduction studies (NCS) showed decreased amplitudes of compound muscle action potentials (CMAPs) (Table 1). Cerebrospinal fluid (CSF) analysis revealed elevated total protein (92 mg/dL), normal cell count (1/lL), and glucose level (72 mg/dL). Intravenous injection of immunoglobulin (IVIg) (400 mg/kg/day for 5 days) was performed and the patient was discharged 2 weeks later with a full recovery. At 54 days after onset of the first episode, exacerbation of lower limbs weakness occurred and he was readmitted. Diarrhea preceded the exacerbation of symptoms. IVIg (400 mg/kg/day for 5 days) was administered again, and the patient fully recovered after 2 weeks. Three years later, the patient was presented with weakness in the lower limbs again 1 week after development of a cough. NCS performed on day 3 showed prolonged distal latencies and decreased amplitudes of CMAPs and decreased amplitudes of sensory nerve action potentials, though those of day 1 were within normal ranges (Table 1). His limbs were moderately weak and deep tendon reflexes were abolished. There was no sensory impairment. CSF analysis revealed elevated total protein (51 mg/dL), normal cell count (1/lL), and glucose level (59 mg/dL). Stool culture showed no growth of Campylobacter jejuni. The symptoms deteriorated and he required respiratory support. IVIg (400 mg/kg/day for 5 days) was given twice and the weakness gradually improved, then 2 months later he was discharged with full recovery. Anti-ganglioside antibody assays of sera obtained during the first and third episodes were performed, and similar anti-ganglioside antibodies were positive. These anti-ganglioside antibodies became negative or declined during the recovery phase (Table 2). We found out two important clinical issues from this case. First, results of anti-ganglioside antibody assays indicate that similar antiganglioside antibodies can be positive despite different types of preceding infections. Thus, we speculate that genetic and immunological host factors may determine not only the clinical phenotype, but also reacted anti-ganglioside antibodies. Second, since the second episode occurred within 2 months after the first episode onset, at that time we considered it to be treatment-related fluctuation & Jumpei Togawa togawa-kyt@umin.org

Polyneuropathy is a common disease and is more prevalent (at least 3 %) in elderly people. However, routine neurological examination of healthy elderly people may show distal sensory loss and absent tendon reflexes, which can obscure the distinction from polyneuropathy.To investigate the relation between age and the prevalence of distal sensory loss, absent tendon reflexes, or muscle weakness, and to ascertain above which age these neurological signs could be considered as normal in ageing.PubMed, Embase, the Cochrane Library, and Current Contents from 1960 until 2004. Reference lists of relevant studies were searched for additional studies, reviews or textbooks.Studies reporting on neurological signs upon routine neurological examination in generally healthy adult persons were considered for inclusion. Two reviewers independently assessed study eligibility and performed study inclusion. Of 629 studies initially identified, 50 (8 %) met the inclusion criteria.Two reviewers independently performed data extraction and assessed study quality based on study design and the rigour by which confounding co-morbidity was excluded.The 50 included studies comprised a total of 9,996 adult persons. Assuming heterogeneity between studies, the prevalence data from different studies were pooled for separate age groups with a random-effects model. In healthy persons older than 60 years the prevalence of absent vibration sense at the big toes (29 % [95 % CI 18 % to 38%]) or ankles (15 % [95 % CI 11 % to 20%]), and absent ankle reflexes (23 % [95 % CI 16 % to 30 %]) was increased.Self-declared healthy adult persons younger than 60 years do not have neurological signs. After the age of 60 absent vibration sense at the big toes or ankles, and absent ankle reflexes are more prevalent, although the majority does not have these neurological signs. It seems more appropriate to apply different diagnostic criteria for polyneuropathy in adult persons younger and older than 60 years.

Dear Sirs,Early-onset familial Alzheimer’s disease (EOFAD) is acondition characterized by early onset dementia associ-ated with a positive family history [1]. Presenilin 1 (PS1)mutations account for the majority cases and comprise anenormous phenotype variability. In special cases, ataxiahas also been reported during the course of the disease, butnot as a major symptom [2].The spinocerebellar ataxias (SCA) are a group of auto-somal dominant inherited neurological disorders, charac-terized by heterogeneous clinical presentations and a broadcombination of cerebellar signs [3]. Cognitive and neuro-psychological deficits have been described in some SCAsubtypes over the last years [4].Herein, we describe a family whose predominant neu-rological features were cerebellar ataxia and memoryimpairment. Bearing in mind that ataxia was one of thepredominant symptoms, genetic investigation was focusedon SCA. In this report, we call attention for atypical pre-sentation of presenilin 1 mutation that might mimick SCA.In Table 1, we summarize the main clinical, demographic,neuroimaging and neuropsychological features of thepatients evaluated.A 37-year-old-man (patient IV.4) presented to our clinicwith a 5-year history of progressive gait disturbances. Onneurological examination, there was axial and appendicularataxia, spasticity and brisk tendon reflexes. The Mini-Mental State Examination (MMSE) score was 13. Brainmagnetic resonance imaging (MRI) disclosed moderatecortical and cerebellar atrophy. His family history wasremarkable, since other family members were affected.Considering cerebellar symptoms as the most relevant,SCA subtypes 1, 2, 3, 6, 10, 17 and dentato-rubro-pallido-luysian (DRPLA) were investigated, and all genetic testsresulted in a negative. Huntington’s disease also was ruledout. For the following 2 years, he developed progressivememory impairment with disorientation in time. Hedeveloped mutism, and his communication is incompre-hensible for no relation to people. Severe stage of dementia(Clinical Dementia Rating-CDR = 3) and neuropsychiatricsymptoms (Neuropsychiatric Inventory-NPI = 45), asaggressiveness, irritability and sleep disturbance, indicate ahigh degree of dependence of daily activities and beingunwieldy for caregivers. Cognitive functions rapidlyworsened and he could not be evaluated by our neuro-psychological battery.A 35-year-old-man (patient IV.11), a cousin of patient 1,came to our hospital with progressive memory impairmentfor the last 6 years and gait instability and dysarthria forthe last 4 years. Neurological examination showed axialand appendicular ataxia, brisk tendon reflexes, and pyra-midal signs. Brain MRI disclosed moderate cortical andcerebellar atrophy. He presented a rapid worsening, and isnow confined to bed. Cognitive functions could not beevaluated, indicating a severe stage of dementia.(CDR = 3; MMSE not testable).A 33-year-old-woman (patient IV.13), a cousin ofpatients 1 and sister of patient 2, complained of progressivememory impairment for the last 4 years and gait instabilityfor the last 3 years. Neurological examination revealed

Lithium is currently used in the prophylaxis and treatment of depression and bipolar disorders. It is rapidly assimilated by gastrointestinal tract and mainly eliminated by the kidney. The narrow therapeutic range and the well-known adverse effects represent two important limits to its utilization in clinical practice: serum levels of lithium should be assessed every 3–6 months, since intoxication may determine renal failure, thyroid dysfunction, cardiac arrhythmias and neurotoxicity including tremor, nystagmus, ataxia, seizures and even coma [1]. Here we describe a case of insidious-onset lithium intoxication resembling a progressive neurodegenerative dementia and requiring differential diagnosis with Creutzfeldt-Jacob disease (CJD). A 60-year-old Italian woman was recently referred to our Unit. She had been affected by bipolar disorder since adolescence, and had been receiving treatment with lithium carbonate (600 mg/day) for 15 years and olanzapine (5 mg/ day) for 5 years. Serum lithium concentration had been regularly assessed and never revealed abnormalities. Moreover, there had been no recent variation of lithium dose. Apart of the psychiatric illness, her clinical history was unremarkable. In the last 2 months, the patient was noted to have decreased cognitive function associated with worsening ataxia and involuntary movements. Also, relatives referred that the patient had become distractible, dysphoric and irritable. On admission, neuropsychological evaluation revealed she was deeply demented, almost speechless, giving erratic or delayed verbal responses to questions. She displayed poverty of thought, disorganization, and attentional impairment. No signs of psychosis were present. Neurological examination revealed ideomotor apraxia, gait ataxia, limb dysmetria and hand myoclonic movements. Routine blood tests were normal, including renal and thyroid function. Electrocardiogram did not reveal alterations. Electroencephalography (EEG) uncovered a significant background slowing with intrusion of biphasic and triphasic slow waves, compatible with cortical and subcortical dysfunction due to toxic/metabolic encephalopathy (Fig. 1a). Brain magnetic resonance imaging showed a chronic vascular encephalopathy with multiple post-ischemic gliotic changes in the periventricular and subcortical white matter. Cerebrospinal fluid analysis did not reveal abnormalities except for mildly increased levels of total-tau protein (347 pg/ml; normal \275) and phosphorylated-tau protein (65 pg/ml; normal\50). Assessment of serum lithium concentration revealed a marked increase at 2.45 mmol/l (therapeutic range 0.6–1.2). Subsequent lithium discontinuation led to a sharp normalization of serum lithium levels and a rapid improvement of cognitive function and ataxia, as well as disappearance of myoclonic jerks. The EEG performed 5 days after drug withdrawal showed partial recovery of background activity and marked decrease of the slow waves (Fig. 1b). On day 10, the patient was discharged with a normal neurological examination. The evaluation of patients with rapidly progressive dementia represents one of the most binding challenges for neurologists [2]. In these patients, taking a drug history is at least as important as performing instrumental and invasive exams. As a matter of fact, a number of medications that are currently used to treat psychiatric and neurological diseases, such as lithium, sodium valproate, carbamazepine A. Mignarri E. Chini A. Rufa R. Rocchi A. Federico M. T. Dotti (&) Department of Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci 2, 53100 Siena, Italy e-mail: dotti@unisi.it

Objectives: (a) To determine the prevalence of unexplained symptoms among newly referred patients in a Dutch academic outpatient clinic for general neurology; (b) To identify factors that can serve as characteristics and possibly as screening instruments for unexplained symptoms in this population. Methods: Observational study, consisting of self-assessment questionnaires. Patients and resident neurologists completed self-designed questionnaires, which included questions about possible features of unexplained symptoms. Patients also completed the Hospital Anxiety and Depression Scale (HADS), evaluating the existence of anxiety and depressive symptoms. Diagnosis of unexplained symptoms was based on the final classification of the patient's symptoms as non-organic, after assessment by a senior neurologist. In the analysis, separate predicting factors and groups of factors were adjusted for age, sex and HADS-score, and analysed as possible characteristics of unexplained symptoms. Results: 35% of the patients (208 total, 174 completed questionnaires) were considered to suffer from unexplained symptoms. Young age (p < 0.001) and female sex (p = 0.007) were significantly associated with unexplained symptoms, high HADS-scores were not (p = 0.10). Characteristics associated with unexplained symptoms were the resident's preliminary impression of symptoms being non-organic, after reading of the referral letter [OR 96.8, 95% confidence interval (95%-CI) 29.7-315, PPV 82%, NPV 96%] and after the first encounter (OR 305, 95%-CI 37.3-2494.6, PPV 83%, NPV 98%), but before the actual history taking and neurological examination. The only other non-demographic characteristic of unexplained symptoms was a visit in order to obtain a second opinion (OR 2.43, 95%-CI 1.15-5.10). Clustering of these factors, however, did not have sufficient predictive power to result in an accurate screening instrument. Conclusions: Unexplained symptoms are common in the neurology outpatient clinic and are to some extent predicted by the physician's preliminary judgement of symptoms. However, history taking and neurological examination remain indispensable for the detection of less obvious organic disorders.

Recently antibodies against neuronal receptors have been identified as cause of a new type of encephalitis. The anti-N-methyl-D-aspartate receptor (anti-NMDA-R) encephalitis is the prototype of these disorders. Patients have a high incidence of teratomata. Removal of teratoma is considered the essential treatment of anti-NMDA-R encephalitis. Here, we aimed to investigate whether neurologically asymptomatic individuals suffering from ovarian teratomata may have positive anti-NMDA-R antibodies to be detected by an established assay. Over a time period of 15 months, all patients suffering from ovarian teratomata without neurological symptoms were included in this prospective study. Twenty consecutive patients were pair matched to patients with other benign ovarian disease and healthy controls. Preoperatively, patients had a gynaecological examination, transvaginal ultrasound, neurological examination and determination of anti-NMDA-R antibodies. None of the patients or controls presented with neurological symptoms. All tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were absent in the group of patients with teratomata as well as in patients with benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies revealed negative findings in well-characterised patients with ovarian teratomata lacking neurological symptoms. Our data support the current clinical practice that a systematic screening for anti-NMDA-R antibodies in teratoma patients is not indicated.

In order to assess nigrostriatal function over time in healthy subjects with substantia nigra hyperechogenicity (SN+) believed to be at higher risk for Parkinson's disease (PD), ten healthy SN+ subjects underwent [(18)Fluoro] Dopa positron emission tomography (PET) twice-at baseline and after a mean of 7.3 years. Neurological examination took place at study inclusion followed by a structured telephone interview focusing on early Parkinsonian symptoms at the time point of second PET study and 3.5 years later. The [(18)Fluoro] Dopa uptake remained unchanged in eight of ten participants. In the other two subjects marked unilateral reduction of putaminal [(18)Fluoro] Dopa uptake ratios appeared over the time, followed by complaints of a clinically manifest PD in one. We suggest that the progressive pathological PET findings in 20 % and PD conversion in 10 % of our cohort may be in accordance with the presumed proportion of SN+ individuals eventually developing PD based on SN+ prevalence of 10 % within the healthy population, being ten times higher than PD prevalence in the age of over 60 years. Our findings hint towards a significance of SN+ indicating a high risk for PD in some extrapyramidally healthy SN+ individuals.

Until recently, dacarbazine (DTIC) was the only registered chemotherapeutic drug for systemic treatment of metastatic melanoma. Patients with progressive disease during DTIC treatment can now also be treated with ipilimumab, a human monoclonal antibody directed against the cytotoxic T-lymphocyte antigen-4 (CTLA-4) receptor. Binding of ipilimumab to the CTLA-4 receptor enhances the immune response of T-lymphocytes, resulting in an offensive against the tumor and an increased median survival of patients with metastatic melanoma [1]. Few data are available on the effect of ipilimumab on central nervous system (CNS) metastases of melanoma [2, 3]. Here, we report a patient with stage IV melanoma, who showed a remarkable response of leptomeningeal metastases (LM) after whole brain radiotherapy (WBRT) and ipilimumab treatment. In January 2009, a 63-year-old woman was diagnosed with lung metastases of a melanoma. DTIC (800 mg/m, q3 weeks) was initiated. In May 2010, after 17 courses, treatment was discontinued due to progression of lung metastases. Concurrently, the patient complained of morning headache, nausea and vomiting. Neurological examination showed no abnormalities. MRI of the brain demonstrated a hyperintense signal in the cerebellar foliae on FLAIR images (Fig. 1a) and slight contrast enhancement of the leptomeninges on T1 images with gadolinium (Fig. 1b). No brain metastases were detected. According to the Dutch guidelines, LM was diagnosed [4–8]. The patient received WBRT (5 9 4 Gy) and low dose dexamethasone. However, her neurological symptoms did not diminish. In June 2010 ipilimumab (3 mg/kg, q3 weeks, four courses) was initiated. After the first course morning headache, nausea, and vomiting disappeared. After three courses the patient developed low grade dermatitis and diarrhea, which both recovered spontaneously. Repeated neurological examination after four courses of ipilimumab showed a slight dexamethasone-induced myopathy and some hearing loss due to the WBRT. The radiological signs of LM on MRI of the brain had disappeared and the CT-thorax showed regression of the lung metastases. On last followup, in October 2011, there were no signs of CNS recurrence on MRI (Fig. 1c, d) and lung metastases were stable. The patient had no complaints and she was near fully active in daily life (WHO 1). This is the first case report describing a metastatic melanoma patient with LM demonstrating a complete clinical and radiological response of LM after WBRT and four courses of ipilimumab. One should consider that, following the USA National Comprehensive Cancer Network (NCCN) CNS tumors section guidelines, CSF examination and MRI of the spine I. Bot (&) D. Brandsma Department of Neuro-oncology, Antoni van Leeuwenhoek Hospital, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands e-mail: i.bot@neuro.umcn.nl

We present a patient with the atypical form of PKAN (pantothenate kinase-associated neurodegeneration, previously called the syndrome of Hallervorden and Spatz) that was caused by a new mutation in the PANK2 gene, with a peculiar type of bradykinesia. A 28-year-old woman was referred after several evaluations by psychiatrists and neurologists for her alleged conversion disorder. She was born after an uneventful pregnancy and delivery in Turkey and came to Holland at the age of 8 years. Since the age of 11 years she suffered from progressive speech problems. Currently, she was almost mute and communicated by typing on her mobile telephone. Furthermore, she suffered from continuous involuntary movements of her arms, difficulties walking, clumsiness of the hands, and frequent falls. History revealed many social problems, including severe domestic violence. Family history revealed consanguine parents, but was negative for neurological or psychiatric conditions. Neurological examination showed an alert woman with unprovoked laughing, who answered by typing on her mobile phone. She was unable to speak except for a single whispered word. She showed frequent repetitive stereotypical movements: stretching, touching the nose, waving and squeezing the hands. The movements appeared as complex motor tics, but no tics were seen in her face. She described the movements as unpleasant and there was no relief after the movements. Requested repetitive hand movements showed an unexpected marked bradykinesia and some dystonic posturing (see online resource for video). Palmomental reflexes were positive. Further neurological examination showed no abnormalities. Neuropsychological examination showed mild impairment of executive functions with decreased mental flexibility and information generation, increased impulsiveness, emotional lability and loss of initiative. A CT scan of the brain showed subtle hyperdensities in the basal ganglia, interpreted as calcifications (Fig. 1), while an MRI scan of the brain showed the ‘eye of the tiger’ sign (Fig. 2) [1]. Genetic analysis revealed a mutation in the PANK2 gene (c.712-714del). We present a patient with atypical PKAN with stereotypical obsessive compulsive movements, mild parkinsonism, severe mutism and a new deletion in the PANK2 gene. Mutism fits well in the clinical spectrum of atypical PKAN. Speech difficulty is either the sole presenting feature or part of the constellation of problems. This includes palilalia, tachylalia/tachylogia, dysarthria to anarthria, hypophonia and difficulty initiating speech [1–3]. In our patient, marked bradykinesia was noted only on specific testing, as she could type remarkably well and quickly. We could not find similar case reports. One patient has been described with stuttering and perseveration in which the speed of verbal neuropsychological tests improved with a laptop [4]. In general, extrapyramidal signs in atypical PKAN cases are less severe than in typical Electronic supplementary material The online version of this article (doi:10.1007/s00415-010-5688-z) contains supplementary material, which is available to authorized users.

We report a case of late-onset predominantly axonal Charcot-Marie-Tooth disease resulting from a novel mutation in the MPZ gene encoding myelin protein zero (P0). Neurological examination, electrophysiological examination and genetic testing were performed on three members of a Finnish family (family A) and one member of a German family (family B). Three other members of the Finnish family were interviewed and genetically tested. Genetic testing was also performed on 95 healthy Finnish controls. Three members in two generations of family A and the member of family B were affected with late-onset axonal more than demyelinating, motor and sensory polyneuropathy. Heterozygous c.316C>T mutation in MPZ leading to p.Arg106Cys in P0 was found in all the affected subjects, but not in the three unaffected members of the Finnish family. None of 95 healthy Finnish controls harbored the mutation. The findings of this study indicate that p.Arg106Cys allele in MPZ causes late-onset predominantly axonal sensory and motor neuropathy.

Item does not contain fulltext Various signs on routine brain MRI can help differentiate between Parkinson's disease (PD) and the various forms of atypical parkinsonism (AP). Here, we evaluate what routine brain MRI contributes to the clinical diagnosis, in both early and advanced disease stages. We performed a prospective observational study in 113 patients with parkinsonism, but without definite diagnosis upon inclusion. At baseline, patients received a structured interview, comprehensive and standardized neurological assessment, and brain MRI. The silver standard diagnosis was made after 3 years of follow-up (PD n = 43, AP n = 57), which was based on disease progression, repeat standardized neurological examination and response to treatment. The clinical diagnosis was classified as having either 'low certainty' (lower than 80%) or 'high certainty' (80% or higher). The added diagnostic yield of baseline MRI results were then studied relative to clinical neurological evaluation at presentation, and at follow-up. Sensitivity and specificity for separating AP from PD were calculated for all potentially distinguishing MRI abnormalities described previously in the literature. MRI abnormalities showed moderate to high specificity but limited sensitivity for the diagnosis of AP. These MRI abnormalities contributed little over and above the clinically based diagnosis, except when the clinical diagnosis was uncertain. For these patients, presence of putaminal or cerebellar atrophy was particularly indicative of AP. Routine brain MRI has limited added value for differentiating between PD and AP when clinical certainty is already high, but has some diagnostic value when the clinical diagnosis is still uncertain. 01 mei 2012

Idiopathic intracranial hypertension (IIH) primarily affects young obese females, and potentially causes visual loss and severe headache. The aim of this experiment is to examine relapse rate and long-term outcome in IIH patients. The methods involved in this experiment include a prospective controlled study of 18 newly diagnosed IIH patients followed for a mean observation period of 21.1 (±8.0) months. Treatment regime included diuretics, dietary recommendations and check-up visits at a dietician. Baseline and follow-up included neurological examination, detailed headache history and comprehensive neuro-ophthalmological examination, including fundus photography, Humphrey visual fields, and measurement of the retinal thickness (RT) and retinal nerve fiber layers (RNFL) by optical coherence tomography (OCT). Relapse was defined as recurrence of either: (1) papilledema or (2) symptoms and demonstrated raised ICP. The result of this experiment is that relapse was found in 28%. Visual function improved from baseline to follow-up and was generally favorable. In patients without relapse of papilledema RT and RNFL were significantly thinner than in healthy controls (p = 0.003 and 0.02), although atrophy was clinically detectable in only one patient. Headache was still present in 67% of the patients at follow-up. Headache was heterogenic and unrelated to relapse. After an initial reduction, weight increased again in the relapse group compared to reduced weight in the non-relapse group (p = 0.013). Thus, the conclusions drawn are that headache was persistent, difficult to classify, and equally represented in relapse and non-relapse patients. Headache was thus a poor marker of active disease. Relapse rate was high and clinically undetectable optic disc atrophy was discovered in apparently well treated IIH patients.

To assess the patterns of dietary (DS) and herbal supplement (HS) use in MS patients, compare use between MS patients and healthy controls and to identify potential interactions with drugs used to treat MS. This study included 279 MS subjects and 161 controls from a study of risk factors in MS. All patients received a neurological examination. All subjects provided responses to a standardized questionnaire administered during an in-person interview. A larger proportion of MS patients (82.1%) compared to controls (60.1%) used one or more DS regularly for at least 3 months (p