[Causes of death in amyotrophic lateral sclerosis : Results from the Rhineland-Palatinate ALS registry]. / Todesursachen bei amyotropher Lateralsklerose : Ergebnisse aus dem ALS-Register Rheinland-Pfalz.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is associated with an increased mortality. Knowledge of possible causes of death could lead to an individualization of the palliative treatment concept and result in a differentiated palliative treatment pathway. Currently, only few systematic data are available on the heterogeneity of causes of death associated with ALS. OBJECTIVE: Analysis of the various causes of death in a prospective population-based German cohort of ALS patients. MATERIAL AND METHODS: Analysis of data of the Rhineland-Palatinate ALS registry in which newly diagnosed patients who had been identified between October 2009 and September 2012 were prospectively enrolled and followed up at regular intervals. From this prospective cohort study the causes of death were elicited based on information provided by the attending physicians, family members and by means of death certificates registered by the regional health authorities in Rhineland-Palatinate. RESULTS: Out of 200 ALS patients registered 148 died between register initiation on 1 October 2009 and the end of follow-up on 30 September 2015 (78 males and 70 females, death rate 74%). The most frequent cause of death was respiratory failure as a consequence of weakness of respiratory muscles (n = 91, 61%). Less frequent causes of death were pneumonia (n = 13, 9%), terminal cachexia (n = 9, 6%) and death from cardiovascular causes including sudden death (n = 9, 6%). Cases of suicide were rare (n = 3, 2%) as were deaths due to concurrent diseases (n = 2). In 21 cases (14%) the exact cause of death could not be clarified. Differences in the causes of death only showed a tendency towards the ALS phenotype. Respiratory failure was the cause of death in all patients with a respiratory phenotype and in 78% of patients with flail arm syndrome. Despite the low number of patients (8%) with additional frontotemporal dementia (FTD) a distinct difference in causes of death between those with and without FTD could be observed. Death due to respiratory failure was less frequent in ALS patients with FTD (33% vs. 65%) while pneumonia was more frequent (27% vs. 7%). CONCLUSION: Respiratory failure was the most frequent cause of death in our cohort of ALS patients. In contrast, pneumonia and nutritional disorders played a less important role as the cause of death. The phenotypic expression of ALS might in part allow the cause of the prospective death to be predicted. Differentiation of ALS phenotypes is an important foundation for patient counseling on the process of dying to be expected and for the determination of an individual palliative concept.

[CNS dysfunction as symptom of internal disease]. / Veränderungen des ZNS als Symptome wichtiger innerer Erkrankungen.

Patients with symptoms and signs of central nervous system dysfunction frequently present to outpatient clinics and emergency departments. Disturbances of consciousness and cognition, headache, vertigo, dizziness or light-headedness, seizures, hemiparesis or hemisensory deficits, and other motor dysfunctions may be due to diseases of internal medicine in up to 50% of cases apart from exclusively neurological diseases. A neurological syndrome oriented analysis of each clinical case allows the exact differential diagnosis of the causes of the disease. A combined approach of internal medicine physicians and neurologists is often warranted.

[Postpartum cerebral venous sinus thrombosis after epidural anaesthesia]. / Sinusvenenthrombose nach geburtshilflicher Epiduralanästhesie.

Cerebral venous sinus thrombosis during pregnancy or puerperium is not a rarity. Nevertheless, it is often misdiagnosed. With the increasing use of regional anaesthesia in obstetrics the differential diagnosis of postdural puncture headache is often difficult. The case of a patient is reported who suffered from both intracranial hypotension and cerebral venous sinus thrombosis in the postpartum period.

Health-related quality of life in segmental dystonia is improved by bilateral pallidal stimulation.

In contrast to generalized dystonia, reports on the effectiveness of pallidal stimulation on quality of life in patients with segmental dystonia are sparse to date. In ten patients with idiopathic segmental dystonia we prospectively evaluated the effect of pallidal stimulation on quality of life using the SF-36 questionnaire. Parallel to the improvement of motor scores, total SF-36 scores and physical and mental health subscores improved significantly at follow-up to a mean of 17 months postoperatively. Thus, pallidal stimulation should be recognized as a promising treatment option in patients with segmental dystonia.

Patterns of reoccurrence of segmental dystonia after discontinuation of deep brain stimulation.

The pattern of reoccurrence of symptoms after discontinuation of deep brain stimulation (DBS) has not been systematically studied in dystonia. Eight patients (mean age (SD) 53.8 (14.4) years) with segmental dystonia at a mean follow-up of 11.3 (4.2) months were studied after implantation of bilateral DBS electrodes in the internal globus pallidus using a standard video protocol and clinical rating scales, immediately and at 2 and 4 h after switching off DBS. Dystonic signs returned sequentially, with a rapid worsening of phasic and a slower worsening of tonic dystonic components. In all patients, phasic dystonic features appeared within a few minutes, whereas the tonic elements of dystonia reoccurred with a more variable delay. Differential clinical effects when withdrawing DBS might reflect its influence on different pathophysiological mechanisms in dystonia.

Chronic spinal cord stimulation in medically intractable orthostatic tremor.

BACKGROUND: Orthostatic tremor with its sense of unsteadiness when standing may have a devastating effect on affected persons. Currently, there are no other treatment options in those who do not respond or who do not tolerate medical treatment. OBJECTIVES: To report on a pilot study on spinal cord stimulation in medically intractable orthostatic tremor. METHODS: Chronic spinal cord stimulation (SCS) was performed in two patients with medically-intractable orthostatic tremor via quadripolar plate electrodes implanted at the lower thoracic spine. The electrodes were connected to implantable pulse generators. RESULTS: Subjective and objective improvement of unsteadiness was achieved within a frequency range of 50 to 150 Hz, and occurred in the presence of stimulation-induced paraesthesia. With optimized stimulation settings polygraphic electromyelogram (EMG) recordings continued to show the typical 14-16 Hz EMG activity. The beneficial effect of SCS was maintained at long-term follow-up. CONCLUSIONS: The results of this pilot study indicate that SCS may be an option in patients with otherwise intractable orthostatic tremor.

Oscillatory pallidal local field potential activity correlates with involuntary EMG in dystonia.

The pathophysiology of dystonia is unclear. The authors recorded local field potentials (LFPs) from deep brain stimulation electrodes implanted in the pallidum of 13 dystonic patients. LFP power correlated with the level of dystonic EMG in the sternocleidomastoid, with maximal positive correlations at the lower contacts of pallidal electrodes. The data suggest that the neuronal synchronization indexed by LFP oscillations in the globus pallidus may be mechanistically linked to dystonic EMG activity.

Bilateral paramedian midbrain infarct: an uncommon variant of the "top of the basilar" syndrome.

Occlusion of the rostral portion of the basilar artery can result in ischaemia of the midbrain and thalami, as well as of the temporal and occipital lobes. The so called "top of the basilar" syndrome manifests clinically as numerous combinations of abnormalities of alertness, sleep-wake cycle, and behaviour and oculomotor or pupillomotor functions. A 67 year old man presented with bilateral internuclear ophthalmoplegia, rubral tremor, and daytime somnolence. He was awake during the night and mostly agitated and aggressive. An ischaemic lesion was visible on the magnetic resonance (MR) image in the central portion of the midbrain just ventral to the aqueduct, clearly affecting the paramedian structures bilaterally. MR angiographic images demonstrated a hypoplastic basilar artery ending in both superior cerebellar arteries. Both posterior cerebral arteries were seen to arise from the corresponding internal carotid arteries via the posterior communicating branches. This unique case of an acute bilateral paramedian infarct represents a highly uncommon variant of the "top of the basilar" syndrome and was due to the affected ischaemic territory--that is, the "distal field" of the variant basilar artery.

Risperidone-responsive segmental dystonia and pallidal deep brain stimulation.

A 67-year-old man with risperidone-responsive segmental dystonia underwent bilateral deep brain stimulation (DBS) of the globus pallidus internus. Prospectively, the authors assessed the Burke-Fahn-Marsden Dystonia Rating Scale in medication (M) and stimulation (S) "on"/"off" states. With DBS at 9 months, the score improved by 86% to 8.5 in M-"on"/S-"on" and 12.5 in M-"off"/S-"on." Studies of the effects of DBS and concomitant medication may be warranted in selected patients treated by DBS for dystonia.

Clinical range and MRI in Creutzfeldt-Jakob disease with heterozygosity at codon 129 and prion protein type 2.

A 68 year old woman with sporadic Creutzfeldt-Jakob disease is described, who neither showed characteristic EEG abnormalities nor a positive test of the neuronal protein 14-3-3 or neuron specific enolase (NSE) in CSF, despite a clinical presentation with ataxia of cerebellar type, rapidly progressive dementia, myoclonus, and marked hyperintense signal abnormalities in the deep cortical layers and the basal ganglia on T2 and diffusion weighted MRI. Moreover she showed atypical clinical features with a syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) and a peripheral sensorimotor polyneuropathy. Whether these disturbances are independent of Creutzfeldt-Jakob disease or a feature of it is discussed. It has recently been shown that in Creutzfeldt-Jakob disease different clinical and pathological phenotypes correlate with the polymorphism at codon 129 of the prion protein gene (PRNP) and the type of the protease resistant fragment that accumulates in the brain. According to the new classification at least six sporadic variants of Creutzfeldt-Jakob disease exist. The molecular genetic analysis showed heterozygosity of PRNP at codon 129 for methionine and valine and the presence of PrP(CJD) type 2 in the brain of this patient. As a new feature of changes on MRI, striking cortical changes of hyperintense signals are described in diffusion weighted as well as T2 weighted MRI that directly correlate with the histomorphological spongy degeneration of the brain in this region. In cases of rapidly progressive dementia, Creutzfeldt-Jakob disease always needs to be considered even if unusual features are present and current diagnostic criteria are not in favour of this disease.

Alcohol-related acute axonal polyneuropathy: a differential diagnosis of Guillain-Barré syndrome.

BACKGROUND: Chronic axonal polyneuropathy is a well-known clinical sequela of excessive alcohol consumption; however, acute axonal polyneuropathy related to alcohol abuse is less well recognized. OBJECTIVE: To describe alcohol-related acute axonal polyneuropathy in 5 chronic alcoholics who developed ascending flaccid tetraparesis and areflexia within 14 days. METHODS: Case series with clinical, laboratory, electrophysiological, and, in 1 patient, biopsy data. RESULTS: All 5 patients consumed a daily average of 250 g of alcohol, and 4 had lost a substantial amount of weight recently. Additional clinical features included painful paresthesia, myalgia, and glove and stocking-type sensory loss. Repeated cerebrospinal fluid examinations failed to show the marked increase of protein concentration with normal cell count typical of Guillain-Barré syndrome, although the protein level was mildly elevated in 1 patient. Blood laboratory findings were consistent with longstanding alcohol abuse. Compound muscle and sensory nerve action potentials were absent or reduced, while conduction velocities were normal or mildly reduced. Three to 4 weeks after onset, needle electromyography displayed moderate to severe fibrillations and positive sharp waves in addition to normal motor unit potentials, indicating an acute axonal polyneuropathy; this was confirmed by sural nerve biopsy in 1 patient. CONCLUSIONS: Excluding other factors, we assume that in these patients the combination of alcohol abuse and malnutrition caused severe acute axonal polyneuropathy. Its distinction from Guillain-Barré syndrome is important because treatment requires balanced diet, vitamin supplementation, and abstinence from alcohol, while immunotherapy may not be indicated.

[Neurologic cause for a respiratory insufficiency]. / Neurologische Ursache einer respiratorischen Insuffizienz.

HISTORY AND CLINICAL FINDING: A 73-year-old man developed progressive respiratory failure within 24 hours, requiring emergency admission for mechanical ventilation. The cause of the dyspnoea and tachypnoea could not be ascertained by routine medical and neurological examination. Neuromuscular disease or a cerebral lesion was considered in the differential diagnosis, together with a cardiovascular cause. INVESTIGATIONS: Neither laboratory tests nor additional investigations (chest radiogram, echocardiography) gave a diagnosis. Magnetic resonance imaging and computed tomography excluded a focal cerebral or spinal lesion or a space-occupying lesion in the region of the phrenic nerve. An electrophysiological tests (EPT) failed to establish a neuromuscular disease. However, when signs of upper motor neurone irritation appeared, more detailed EPTs, also of the muscles of breathing, provided the diagnosis of amyotrophic lateral sclerosis (ALS). TREATMENT AND COURSE: Symptomatic treatment with pyridostigmine made it possible gradually to wean the patients off the ventilator so that he could be sent home on intermittent mechanical ventilation. CONCLUSION: In case of acute respiratory failure without cardiopulmonary cause motoneurone disease with initial involvement of respiratory musculature should be considered, even in the absence of clinical signs, and special electrophysiological tests may be necessary to recognize the underlying disease.

Acute multifocal motor neuropathy with early spontaneous recovery: a distinct syndrome from Guillain-Barré syndrome?

We describe a case of acute multifocal motor neuropathy with normal sensory conduction studies in the nerve segments of severe motor conduction block. Antiganglioside antibodies were not detected in serum and the patient recovered spontaneously. The clinical picture and course of time of the illness allowed the diagnosis of a Guillain-Barré syndrome (GBS). The electrophysiological findings closely matched the typical findings of chronic multifocal motor neuropathy with persistent conduction block. From these similarities, we conclude that acute and chronic forms of acquired demyelinating motor neuropathies have to be accepted as variants of acute GBS and chronic inflammatory demyelinating polyneuropathy (CIDP), respectively. We suggest that the conduction block cannot always be attributed to antiganglioside antibodies, as chronic cases without antiganglioside antibodies have also been reported and further elevation of antibody titres has been seen after spontaneous recovery.