Multifocal motor neuropathy as a mimic of amyotrophic lateral sclerosis: Serum neurofilament light chain as a reliable diagnostic biomarker.

INTRODUCTION/AIMS: The clinical presentation of multifocal motor neuropathy (MMN) may mimic early amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron (LMN) involvement, posing a diagnostic challenge. Both diseases have specific treatments and prognoses, highlighting the importance of early diagnosis. The aim of this study was to assess the diagnostic value of serum neurofilament light chain (NfL) in differentiating MMN from LMN dominant ALS. METHODS: NfL was measured in serum in n = 37 patients with MMN and n = 37 age- and sex-matched patients with LMN dominant ALS, to determine the diagnostic accuracy. Clinical and demographic data were obtained at the time of NfL sampling. RESULTS: Serum NfL concentration was significantly lower in MMN patients compared to ALS patients (mean 20.7 pg/mL vs. 59.4 pg/mL, p < .01). NfL demonstrated good diagnostic value in discriminating the two groups (AUC 0.985 [95% CI 0.963-1.000], sensitivity 94.6%, specificity 100%, cut-off 44.00 pg/mL). DISCUSSION: NfL could be a helpful tool in differentiating MMN from LMN dominant ALS in those patients in whom electrophysiological and clinical examinations remain inconclusive early in the diagnostic process.

Multifocal motor neuropathy in Austria: a nationwide survey of clinical features and response to treatment.

BACKGROUND AND OBJECTIVES: Multifocal motor neuropathy (MMN) is a rare neuropathy and detailed descriptions of larger patient cohorts are scarce. The objective of this study was to evaluate epidemiological, clinical, and laboratory features of MMN patients and their response to treatment in Austria and to compare these data with those from the literature. METHODS: Anonymized demographic and clinical data about MMN patients until 31.12.2017 were collected from registered Austrian neurologists. Exploratory statistics on clinical and laboratory features as well as treatment regimens and responses were performed. RESULTS: 57 Patients with MMN were identified, resulting in a prevalence of 0.65/100.000. Mean age of onset was 44.1 ± 13.1 years, the diagnostic delay 5.5 ± 8.4 years. In 77% of patients, symptom onset was in the upper limbs, and in 92%, it occurred in distal muscles. Proximal onset was never observed in the lower limbs. At the final follow-up, the majority of patients had atrophy (88%) in affected regions. Definite motor conduction blocks (CB) were found in 54 patients. Anti-GM1-IgM antibodies were present in 43%. Treatment with intravenous immunoglobulins improved muscle strength and INCAT score initially, but at last follow-up, both scores deteriorated to values before treatment. DISCUSSION: The findings of the present study corroborate the previous findings in MMN. Onset typically occurs in the upper limbs and mostly distal, CBs are found in the majority of cases, while anti-GM1-IgM antibodies are detected in only approximately 40%. Our study underlines that the initial good response to treatment fades over time.

Secondary dementia due to Lyme neuroborreliosis.

Dementia-like syndromes are rare manifestations of Lyme neuroborreliosis. The clinical patterns are summarized using our own cases and case reports from the literature, which were diagnosed as definite Lyme neuroborreliosis according to the European guidelines. The cases disclose signs of subcortical dementia that occur more rapidly than in patients suffering from primary dementia. Gait disturbances early in the disease course is another frequently observed characteristic feature. The response to 2-4 weeks of antibiotic treatment with ceftriaxone was excellent. There were no indications for a prolonged antibiotic treatment. It is essential to be aware of this manifestation of Lyme neuroborreliosis, because early antibiotic treatment will prevent permanent sequelae that may occur throughout the further course of the untreated disease.

Distinct Niemann-Pick Disease Type C Clinical, Cytological, and Biochemical Phenotype in an Adult Patient With 1 Mutated, Overexpressed NPC1 Allele

Abstract Niemann-Pick disease type C (NP-C) is a rare autosomal-recessive neurovisceral lysosomal storage disease. We report on a juvenile onset, now 25-year-old female patient with typical neurologic symptoms, including vertical gaze palsy, of NP-C. The diagnosis was supported by a positive filipin test ("variant biochemical phenotype" of cholesterol accumulation) in cultured fibroblasts, high numbers of "Niemann-Pick cells" in the bone marrow, and 1 positive out of 3 NP-C biomarkers tested, but NP-C was not definitely confirmed genetically. She showed only 1 known NPC1 variant (3 bp deletion in exon 18; p.N916del); this allele, however, being distinctly overexpressed at the messenger RNA level as compared to the wild-type allele, as a not as yet clarified (copathogenic?) phenomenon. The patient's mother, also carrying the p.N916del allele but without overexpression, has a chronic inflammatory disease of the central nervous system classified as multiple sclerosis. However, her severe clinical phenotype includes some signs also consistent with NP-C. The laboratory diagnosis of NP-C can be challenging in detecting novel disease constellations.

Aldehyde dehydrogenase 2 in sporadic Parkinson's disease.

Aldehyde dehydrogenases (ALDH) play a key role in neuronal protection. They exert this function by metabolizing biogenic amine-related aldehydes, e.g. 3,4-dihydroxyphenylacetaldehyde (DOPAL), and by protecting neurons against aldehyde- and oxidative stress-related neurotoxicity. The role of these different isoenzymes has been discussed in other neurodegenerative disorders before. It is somewhat surprising that only few studies have investigated their role in the aetiology of Parkinson's disease (PD), in both the degeneration of dopaminergic neurons and the formation of Lewy bodies. Earlier studies report severe alterations of the cytosolic isoform of ALDH expression (ALDH 1A1) in the substantia nigra of patients with PD. However, there are no data regarding the activity of ALDH 2 located at the inner mitochondrial membrane. Since mitochondrial dysfunctions are hypothesized to be of importance in the aetiology of PD we have examined the enzymatic activity of mitochondrial ALDH 2 in post-mortem putamen and frontal cortex of patients with PD and controls. We found that mitochondrial ALDH 2 activity in contrast to the frontal cortex was significantly increased in the putamen of patients with PD compared to controls.

Neuromyelitis optica in Austria in 2011: to bridge the gap between neuroepidemiological research and practice in a study population of 8.4 million people.

BACKGROUND: In 2008 the Austrian Task Force for Neuromyelitis Optica (NMO) started a nation-wide network for information exchange and multi-centre collaboration. Their aim was to detect all patients with NMO or NMO spectrum disorders (NMO-SD) in Austria and to analyse their disease courses and response to treatment. METHODS: (1) As of March 2008, 1957 serum samples (of 1557 patients) have been tested with an established cell based immunofluorescence aquaporin-4 antibody (AQP4-ab) assay with a high sensitivity and specificity (both >95%). All tests were performed in a single reference laboratory (Clinical Dept. of Neurology of the Innsbruck Medical University). (2) A nation-wide survey with several calls for participation (via email newsletters, articles in the official journal of the Austrian Society of Neurology, and workshops) was initiated in 2008. All collected data will be presented in a way that allows that every individual patient can be traced back in order to ensure transparency and to avoid any data distortion in future meta-analyses. The careful and detailed presentation allows the visualization and comparison of the different disease courses in real time span. Failure and response to treatment are made visible at one glance. Database closure was 31 December 2011. All co-operators were offered co-authorship. RESULTS: All 71 NMO- or NMO-SD patients with AQP4-ab positivity (age range 12.3 to 79.6 years) were analysed in detail. Sex ratio (m:f = 1:7) and the proportion of patients without oligoclonal bands in cerebrospinal fluid (86.6%) were in line with previously published results. All identified patients were Caucasians. CONCLUSIONS: A nationwide collaboration amongst Austrian neurologists with good network communications made it possible to establish a database of 71 AQP4-ab positive patients with NMO/NMO-SD. This database is presented in detail and provides the basis for further studies and international cooperation in order to investigate this rare disease.

Spinal cord lesions in patients with neuromyelitis optica: a retrospective long-term MRI follow-up study.

Neuromyelitis optica (NMO) is characterised by a particular pattern of the optic nerves and the spinal cord. Long-term MRI follow-up studies of spinal NMO lesions are rare, or limited by short observation periods. In nine patients with definite NMO or recurrent longitudinally extensive transverse myelitis (LETM) with NMO-IgG serum antibodies, repeated MRI examinations of the spine were carried out over a period of up to 11 years and evaluated regarding the changes over time in this retrospective study. In eight patients spinal cord lesions were located centrally, involving the grey and white matter. In the first examination after clinical onset changes resembled a stroke of the anterior spinal artery in two patients. Symmetrical signal alterations within the grey matter were observed. In one patient this pattern was transient, but it remained in the other. During the chronic stage, either a variable degree of spinal cord atrophy and high signal alterations, or almost complete remission of the lesions, was observed. Spinal MRI of patients with NMO myelitis can resemble a stroke. MRI of acute NMO stages did not allow a prediction of the clinical outcome. To a variable degree, NMO left behind typical defects which correlated with the clinical outcome.

Altered glial cell line-derived neurotrophic factor (GDNF) concentrations in the brain of patients with depressive disorder: a comparative post-mortem study.

INTRODUCTION: A growing body of evidence suggests that the glial cell line-derived neurotrophic factor (GDNF) is involved in the aetiopathology of mood disorders. GDNF is a neurotrophic factor from the transforming growth factor-beta-family, playing a role in cell development and function in the limbic system. This is the first study to examine GDNF concentration in different brain regions of patients with depressive disorder (DD). MATERIAL AND METHODS: We used sandwich-ELISA-technique to ascertain GDNF concentration and Lowry assay for overall protein levels in post-mortem brain tissue of 7 patients with recurrent depressive disorder and 14 individuals without any neurological or psychiatric diagnoses. We included cortical regions as well as limbic area's (hippocampus, entorhinal cortex) basal ganglia (putamen, caudate nucleus), thalamus and cingulated gyrus. RESULTS: We found a significant increase in GDNF concentration in the parietal cortex of patients with DD compared to the control group. In other regions the trend of an increased GDNF concentration did not reach statistical difference. DISCUSSION: This proof of concept study supports previous findings of an alteration of the GDNF in patients with depressive disorder. However, for the first time a significant increase of GDNF in a cortical brain area was found in DD.

Evidence for oxidative stress in the frontal cortex in patients with recurrent depressive disorder--a postmortem study.

Prefrontal cortical (PFC) and hippocampal (HI) volume reductions have been consistently found in patients with recurrent depressive disorder (DD). Here we examine the possibility that oxidative stress, widely implicated in neuronal cell damage, may contribute to these brain structural changes. We compared manganese (Mn) and copper/zinc (Cu/Zn) superoxide dismutase (SOD) coenzyme concentrations in postmortem PFC and hippocampal brain tissue from 7 patients with DD and 7 neuropsychiatrically healthy controls using sandwich-type enzyme-linked immunosorbent assay (ELISA) technique. The concentration of Cu/Zn-SOD was significantly increased in the PFC but not in the hippocampus of patients. There was no significant change in Mn-SOD enzyme concentration in either region. Our findings contribute to the growing body of evidence implicating oxidative stress in the pathophysiology of depressive disorder.

Feline orthopoxvirus infection transmitted from cat to human.

We report the case of a 56-year-old female patient who presented with an inflamed, ulcerated lesion on the left side of her neck after contact (scratch) with a cat living in the patient's house. Satellite lesions developed despite local treatment and parenteral clindamycin. Histopatholgic examination and the Tzanck test showed evidence of a viral infection. Subsequent transmission electron microscopy of scrap tissue and material from a fresh pustule exhibited multiple typical poxvirus particles, predominantly in remnants of scaled-off layers of degenerated keratinocytes, and virus particles in intermingled phagocytes, leading to the diagnosis of feline Orthopoxvirus (cowpox virus) infection. These results were verified by polymerase chain reaction and sequencing. Concern has been raised as to whether discontinuation of smallpox vaccine would cause an increase in Orthopoxvirus infection, but this has not yet shown to be the case.