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Objective Hematoma enlargement (HE) is associated with clinical outcomes after supratentorial intracerebral hemorrhage (ICH). This study evaluates whether HE characteristics and association with functional outcome differ in deep versus lobar ICH. Methods Pooled analysis of individual patient data between January 2006 and December 2015 from a German‐wide cohort study (RETRACE, I + II) investigating ICH related to oral anticoagulants (OAC) at 22 participating centers, and from one single‐center registry (UKER‐ICH) investigating non‐OAC‐ICH patients. Altogether, 1954 supratentorial ICH patients were eligible for outcome analyses, which were separately conducted or controlled for OAC, that is, vitamin‐K‐antagonists (VKA, n = 1186) and non‐vitamin‐K‐antagonist‐oral‐anticoagulants (NOAC, n = 107). Confounding was addressed using propensity score matching, cox regression modeling and multivariate modeling. Main outcomes were occurrence, extent, and timing of HE (>33%/>6 mL) and its association with 3‐month functional outcome. Results Occurrence of HE was not different after deep versus lobar ICH in patients with non‐OAC‐ICH (39/356 [11.0%] vs. 36/305 [11.8%], P = 0.73), VKA‐ICH (249/681 [36.6%] vs. 183/505 [36.2%], P = 0.91), and NOAC‐ICH (21/69 [30.4%] vs. 12/38 [31.6%], P = 0.90). HE extent did not differ after non‐OAC‐ICH (deep:+59% [40–122] vs. lobar:+74% [37–124], P = 0.65), but both patients with VKA‐ICH and NOAC‐ICH showed greater HE extent after deep ICH [VKA‐ICH, deep: +94% [54–199] vs. lobar: +56% [35–116], P

Amantadine is frequently used in addition to dopaminergic substances like dopamine agonists or L-Dopa in advanced Parkinson disease (PD). However, adverse effects like hallucinations limit its use. PD patients developing severe psychotic symptoms upon treatment with either dopaminergic substances and/or amantadine need to stop intake of any psychotropic substance. Here, we report the case of a 71-year-old PD patient without previously known cognitive impairment. He presented with drug-induced psychotic symptoms due to changes in his therapeutic regimen (increase in COMT inhibitors, newly introduced MAO B inhibitors). Also, amantadine had been part of his long-term medication for more than 2 years. The severity of his psychotic symptoms required a L-Dopa monotherapy. After changing his medication, the patient developed severe delirium that resolved rapidly after i.v. amantadine infusion, suggesting an amantadine withdrawal syndrome. Amantadine withdrawal syndrome is a rare adverse event that may present even in PD patients without cognitive impairment. This case report highlights the need for a gradual withdrawal of amantadine even if acute and severe psychotic symptoms are present. Moreover, this is the first report of a cognitively unimpaired patient developing an amantadine withdrawal syndrome.

Background Clobazam (CLB) is a well characterized antiepileptic drug (AED) that differs from other benzodiazepines by its basic chemical structure and pharmacodynamic properties. Only one previous study examined the efficacy of CLB as add-on therapy in refractory status epilepticus (RSE). Methods We analyzed RSE episodes treated in our institution between 2001 and 2012. Successful treatment with CLB was scored if CLB was the last AED added to therapy before RSE termination. We assessed the differences between patients with and without CLB and correlated CLB with outcome. Among patients treated with CLB, we studied responders and non-responders and compared our CLB cohort with recently published data. Results CLB was part of the AED regimen in 24/70 (34.3 %) RSE episodes. In six of these (25.0 %) RSE resolution was attributed to CLB. Baseline characteristics of episodes with and without CLB treatment showed no significant differences and RSE termination rates were very similar (83.3 % vs. 80.4 %). CLB was administered in clinically more complex RSE with longer RSE duration and worse outcome, but CLB was not related independently to outcome. Comparison of our results with previously published data revealed that baseline characteristics as well as CLB maintenance doses and time of treatment initiation were similar in both cohorts. CLB was less frequently the last AED added to RSE therapy in our patients indicating a lower treatment success rate than previously reported. Conclusions CLB represents a reasonable AED and promising add-on agent for treatment of RSE. However, rates of successful CLB response were substantially lower than in a recently published study. Differing RSE characteristics and treatment strategies may account for the discrepancy between study results, as RSE etiologies and seizures types associated with unfavorable prognosis were more common in our cohort, while anesthetics tended to be less frequently applied to achieve seizure control.

Im Jahr 2004 sind Mutationen im Gen LRRK2 als Ursache für eine autosomal-dominant vererbte Form des Parkinsonismus identifiziert worden und gelten inzwischen als häufigste genetische Ursache sowohl familiärer als auch sporadischer Formen des idiopathischen Parkinson-Syndroms. Die Betroffenen zeichnen sich einerseits durch ein für Morbus Parkinson typisches klinisches Erscheinungsbild aus, weisen andererseits jedoch als besonderes, in dieser Form einzigartiges Merkmal die verschiedensten neuropathologischen Veränderungen auf, die bisher unterschiedlichen Gruppen neurodegenerativer Erkrankungen zugeordnet wurden. So beobachtet man neben neuronalem Zelluntergang in der Substantia nigra mit oder ohne Lewy-Körperchen sogar Tau-positive Einschlüsse in einer Ausprägung, welche die diagnostischen Kriterien einer Progressiven Supranukleären Blickparese erfüllt. In Anbetracht dieser Erkenntnisse kann eine zentrale Rolle von LRRK2 in der Entstehung neurodegenerativer Prozesse vermutet und auf diese Weise eine rationale Grundlage für die Untersuchung seines Beitrags in der Entstehung weiterer neurodegenerativer Erkrankungen, u.a. der atypischen Parkinson-Syndrome, gelegt werden. Im Rahmen dieser Arbeit wurden DNA-Proben von MSA- und PSP-Patienten auf bereits bekannte LRRK2-Mutationen gescreent. Die Untersuchung der PSP-Proben beschränkte sich, gestützt auf der Beschreibung PSP-artiger neuropathologischer Veränderungen eines R1441C-Mutationsträgers, auf Exon 31 von LRRK2. Die MSA-Proben hingegen wurden auf Mutationen in Exon 41 von LRRK2 untersucht, da bei einem Mitglied der Sagamihara-Familie mit neuropathologisch gesicherter MSA die I2020T-Mutation gefunden wurde. Des Weiteren legt die Häufigkeit der ebenfalls in Exon 41 lokalisierten G2019S-Mutation beim idiopathischen Parkinson-Syndrom deren besondere Bedeutung in der Entstehung von Synukleinopathien nahe. Bei keinem Patienten konnten im Rahmen dieser Studie LRRK2-Mutationen nachgewiesen werden. Die Ergebnisse der vorliegenden Arbeit bestätigen und erweitern diesbezüglich die derzeitige Datenlage. Zum jetzigen Zeitpunkt ist es, bis auf vereinzelte, in ihrer Bedeutung schwer einzustufende Ausnahmen somit weder gelungen, MSA- noch PSP-Fälle direkt mit Mutationen in LRRK2 in Verbindung zu bringen. Eine potentielle Rolle von LRRK2 in der Entstehung dieser beiden Erkrankungen kann dennoch nicht ausgeschlossen werden, zumal sich die bisherigen Studien meist auf wenige Abschnitte von LRRK2 beschränkt haben und aus diesem Grund Aussagen über den Rest dieses riesigen Gens nicht getroffen werden können. Man kann erwarten, dass umfassendere Untersuchungen hierbei in Zukunft weitere Klarheit schaffen werden. Außerdem gibt es viele Hinweise darauf, dass LRRK2 eine übergeordnete Position in einem Netzwerk interagierender Proteine einnimmt, in dem Störungen zu neurodegenerativen Prozessen führen können. LRRK2-Mutationen können folglich als auslösende Ereignisse in einer zu Neurodegeneration mit variablen pathologischen Veränderungen führenden Kaskade angesehen werden und somit in der Ätiologie verschiedener neurodegenerativer Erkrankungen involviert sein. Aus diesem Grund ist es möglich, dass die genauere Erforschung von LRRK2 Erkenntnisse erbringen wird, die auf verschiedene Erkrankungen übertragbar sind. Es bleibt zu hoffen, dass sich daraus in Zukunft neue diagnostische und therapeutische Möglichkeiten ergeben werden. In 2004, mutations in a gene called LRRK2 were identified as a cause of autosomal dominantly inherited parkinsonism and today are considered the most frequent genetic cause of both familial as well as sporadic forms of Parkinson’s disease. Patients harboring LRRK2 mutations on the one hand have a clinical presentation typical of idiopathic Parkinson’s disease, on the other hand, however, feature a special and unique variety of neuropathological alterations which used to be considered hallmarks of different types of neurodegenerative disorders. Besides neuronal loss in the substantia nigra with or without Lewy bodies, even Tau-positive inclusions meeting the diagnostic criteria of progressive supranuclear palsy can be seen. Given these findings, a central position of LRRK2 in the etiology of neurodegenerative processes in general can be assumed, which provides a rational basis for further research on its role in the development of other neurodegenerative disorders such as atypical parkinsonian syndromes. In this study, DNA samples of MSA and PSP patients were screened for known LRRK2 mutations. Based on the description of PSP-like neuropathological alterations in a R1441C mutation carrier, DNA samples of PSP patients were screened for mutations in exon 31 of LRRK2. As a member of the Sagamihara family with neuropathologically confirmed MSA was found to carry the I2020T mutation, DNA samples of MSA patients were analyzed for mutations in exon 41 of LRRK2. Furthermore, another mutation in this exon, G2019S, occurs frequently in idiopathic Parkinson’s disease suggesting its special importance in the etiology of synucleinopathies. No LRRK2 mutations could be found in any patient screened in this study. The results of this work confirm and expand previous knowledge. To date, with a few exceptions of uncertain relevance, no MSA or PSP case could directly be associated with mutations in LRRK2. Still, a potential role of the gene in the development of these disorders cannot be excluded completely, as studies performed so far mainly focused on a few sections of LRRK2, so that statements on the rest of this large gene cannot be made. It can be expected that more extensive studies will help calrify its role in the future. Furthermore, there is evidence that LRRK2 may have a superordinate position in a network of interacting proteins which, when disturbed, may lead to neurodegenerative processes. Thus, LRRK2 mutations can be considered upstream events in a cascade leading to neurodegeneration with variable pathological changes and in that way be involved in the etiology of diverse neurodegenerative disorders. For that reason, further exploration of LRRK2 may yield findings transferable to various diseases. It remains to be hoped that this may lead to new diagnostic and therapeutic options in the future.