An unusual presentation of Listeria monocytogenes rhombencephalitis

We describe a case of 52-year-old woman with a medical history of Crohn's disease presented abrupt fever, asymmetrical multiple cranial nerve palsies and focal neurological symptoms localized to the brainstem. The patient was initially diagnosed with ischaemic stroke, because of acute clinical course and results of neuroimaging. Cerebrospinal fluid analysis revealed mild infection with negative Gram staining and culture. Final diagnosis of Listeria monocytogenes brainstem infection (rhombencephalitis) was set up on the basis of further clinical course and positive blood cultures. Listerial rhombencephalitis should be kept in mind in immunocompromised adult patients who develop fever, asymmetrical multiple cranial nerve palsies and focal neurological symptoms localized to the brainstem even without typical neuroimaging, cerebrospinal fluid findings and negative cultures. Early diagnosis and adequate antibiotic treatment is of crucial importance

An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury

Current therapies to limit the neural tissue destruction following the spinal cord injury are not effective. Our recent studies indicate that the injury to the white matter of the spinal cord results in a severe inflammatory response where macrophages phagocytize damaged myelin and the fluid-filled cavity of injury extends in size with concurrent and irreversible destruction of the surrounding neural tissue over several months. We previously established that a high dose of 4mg/rat of dexamethasone administered for 1 week via subdural infusion remarkably lowers the numbers of infiltrating macrophages leaving large amounts of un-phagocytized myelin debris and therefore inhibits the severity of inflammation and related tissue destruction. But this dose was potently toxic to the rats. In the present study the lower doses of dexamethasone, 0.125–2.0mg, were administered via the subdural infusion for 2 weeks after an epidural balloon crush of the mid-thoracic spinal cord. The spinal cord cross-sections were analyzed histologically. Levels of dexamethasone used in the current study had no systemic toxic effect and limited phagocytosis of myelin debris by macrophages in the lesion cavity. The subdural infusion with 0.125–2.0mg dexamethasone over 2 week period did not eliminate the inflammatory process indicating the need for a longer period of infusion to do so. However, this treatment has probably lead to inhibition of the tissue destruction by the severe, prolonged inflammatory process

Spinocerebellar Ataxia Types 1, 2, 3 and 6: the Clinical Spectrum of Ataxia and Morphometric Brainstem and Cerebellar Findings

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Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Diagnostyka i leczenie padaczki — wytyczne Sekcji Padaczki Polskiego Towarzystwa Neurologicznego

W ostatnich latach opublikowano wiele rekomendacji oraz standardów diagnostyki i leczenia chorych z padaczką. Mimo różnic między przedstawionymi zaleceniami podstawowe zasady dotyczące stosowania leków przeciwpadaczkowych są wspólne i dokładnie określone. W Polsce w ostatnich kilku latach zasady refundacji istotnie się zmieniły. Wprowadzone zmiany umożliwiają wybór terapii zgodnie z dostępną wiedzą wynikającą z przeprowadzonych badań klinicznych oraz doświadczenia nagromadzonego w praktyce klinicznej. Podstawowe znaczenie dla uzyskania pozytywnego efektu stosowanej terapii ma prawidłowo przeprowadzona diagnostyka. Właściwe rozpoznanie odpowiedniego typu napadów padaczkowych lub określonego zespołu padaczkowego warunkuje skuteczność terapii. W artykule przedstawiono aktualne zalecenia dotyczące diagnozowania i leczenia padaczki zarówno na etapie wstępnym, jak i u osób z podejrzeniem padaczki lekoopornej. Dokonano również adaptacji rekomendacji międzynarodowych do warunków systemu opieki neurologicznej funkcjonującego w Polsce. Sekcja Padaczki Polskiego Towarzystwa Neurologicznego opracowała niniejsze rekomendacje na podstawie dostępnych danych naukowych oraz uwarunkowań refundacyjnych obowiązujących w Polsce na 2022 rok

Prolonged Subdural Infusion of Kynurenic Acid Is Associated with Dose-Dependent Myelin Damage in the Rat Spinal Cord.

Kynurenic acid (KYNA) is the end stage metabolite of tryptophan produced mainly by astrocytes in the central nervous system (CNS). It has neuroprotective activities but can be elevated in the neuropsychiatric disorders. Toxic effects of KYNA in the CNS are unknown. The aim of this study was to assess the effect of the subdural KYNA infusion on the spinal cord in adult rats.A total of 42 healthy adult rats were randomly assigned into six groups and were infused for 7 days with PBS (control) or 0.0002 pmol/min, 0.01 nmol/min, 0.1 nmol/min, 1 nmol/min, and 10 nmol/min of KYNA per 7 days. The effect of KYNA on spinal cord was determined using histological and electron microscopy examination. Myelin oligodendrocyte glycoprotein (MOG) was measured in the blood serum to assess a degree of myelin damage.In all rats continuous long-lasting subdural KYNA infusion was associated with myelin damage and myelin loss that was increasingly widespread in a dose-depended fashion in peripheral, sub-pial areas. Damage to myelin sheaths was uniquely related to the separation of lamellae at the intraperiod line. The damaged myelin sheaths and areas with complete loss of myelin were associated with limited loss of scattered axons while vast majority of axons in affected areas were morphologically intact. The myelin loss-causing effect of KYNA occurred with no necrosis of oligodendrocytes, with locally severe astrogliosis and no cellular inflammatory response. Additionally, subdural KYNA infusion increased blood MOG concentration. Moreover, the rats infused with the highest doses of KYNA (1 and 10 nmol/min) demonstrated adverse neurological signs including weakness and quadriplegia.We suggest, that subdural infusion of high dose of KYNA can be used as an experimental tool for the study of mechanisms of myelin damage and regeneration. On the other hand, the administration of low, physiologically relevant doses of KYNA may help to discover the role of KYNA in control of physiological myelination process

Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6

Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The schematic presentation of intrathecal catheter placement.

<p>A–C7 –Th1 level of spinal cord, B–intrathecal catheter, C–a place of surgery.</p

Electron micrographs of severe demyelination in the area of the fasciculus gracilis of the dorsal column in the rat treated with the intrathecal infusion of 10 nmol/min of kynurenic acid (KYNA) per 5 days.

<p>A–in the area of severe demyelination, most of axons are naked, there are 3 astrocytes (As), one oligodendrocyte (OL) and a small blood vessel (bv). B–on higher magnification, the oligodendrocyte appears to have a compact cytoplasm devoid of processes; it is surrounded by many naked axons, some of the diameter greater than 2 μM (asterices) and a few myelinated axons. Size bars; A– 10 μM, B– 2 μM.</p

Electron micrographs of damaged myelin sheaths from the spinal cord of rats infused intrathecally with kynurenic acid (KYNA) for 7 days.

<p>A–an area from the dorsal column of a rat infused with 0.01 nmol/min of KYNA with an astrocyte (As) and an oligodendrocyte (OL) surrounded by damaged myelin sheaths. B–in this detail of A delineated by the white box, a segment of well compacted thick myelin sheath (Ms) passes into a segment were all lamellae are widely separated due to disintegration of compaction at the intraperiod line indicated by arrows. C–an example of a damaged myelin sheath from a single axon (Ax) from the lateral column of the rat infused with 10 nmol/min KYNA were a few well compacted lamellae (white double headed arrows) are widely separated by uncompacted lamellae (black arrows). D–in the lateral column of a rat infused with 1 nmol/min of KYNA, an axon (Ax) has a damaged myelin with segmental loss of compaction due to separation of lamellae at the intraperiod line (white arrow). There is a well-compacted thick myelin sheath (Ms) in the adjacent axon. E–lateral column from a rat infused with 0.0002 pmol/min of KYNA per 7 days, with multiple myelin sheaths showing the segmental loss of compaction and one oligodendrocyte (OL). The box indicates the area displayed in higher magnification in F–with two axons (Ax) surrounded by uncompacted myelin lamellae. Size bars; A, E– 5 μM, B, C, D– 100 nM, F– 1 μM.</p