Guideline "Transient Global Amnesia (TGA)" of the German Society of Neurology (Deutsche Gesellschaft für Neurologie): S1-guideline.

INTRODUCTION: In 2022 the DGN (Deutsche Gesellschaft für Neurologie) published an updated Transient Global Amnesia (TGA) guideline. TGA is characterized by a sudden onset of retrograde and anterograde amnesia for a period of one to a maximum of 24 h (with an average of 6 to 8 h). The incidence is estimated between 3 and 8 per 100,000 population/year. TGA is a disorder that occurs predominantly between 50 and 70 years. RECOMMENDATIONS: The diagnosis of TGA should be made clinically. In case of an atypical clinical presentation or suspicion of a possible differential diagnosis, further diagnostics should be performed immediately. The detection of typical unilateral or bilateral punctate DWI/T2 lesions in the hippocampus (especially the CA1 region) in a proportion of patients proves TGA. The sensitivity of MRI is considered higher when performed between 24 and 72 h after onset. If additional DWI changes occur outside the hippocampus, a vascular etiology should be considered, and prompt sonographic and cardiac diagnostics should be performed EEG may help to differentiate TGA from rare amnestic epileptic attacks, especially in recurrent amnestic attacks. TGA in patients < 50 years of age is a rarity, therefore it is mandatory to rapidly search for other causes in particular in younger patients. The cause of TGA is still unknown. Numerous findings in recent years point to a multifactorial genesis. Because the pathomechanism of TGA is not yet clearly known, no evidence-based therapeutic or prophylactic recommendations can be made. CONCLUSIONS: There is no evidence for chronic sequelae of TGA with respect to cerebral ischemia, chronic memory impairment, or the onset of dementia-related syndromes.

Spelling interface using intracortical signals in a completely locked-in patient enabled via auditory neurofeedback training.

Patients with amyotrophic lateral sclerosis (ALS) can lose all muscle-based routes of communication as motor neuron degeneration progresses, and ultimately, they may be left without any means of communication. While others have evaluated communication in people with remaining muscle control, to the best of our knowledge, it is not known whether neural-based communication remains possible in a completely locked-in state. Here, we implanted two 64 microelectrode arrays in the supplementary and primary motor cortex of a patient in a completely locked-in state with ALS. The patient modulated neural firing rates based on auditory feedback and he used this strategy to select letters one at a time to form words and phrases to communicate his needs and experiences. This case study provides evidence that brain-based volitional communication is possible even in a completely locked-in state.

Bilateral Fascicular Third Nerve Palsy in Posterior Circulation Stroke.

Third nerve palsy is bilateral in only about 10% of cases, of which one in five cases is due to brainstem stroke. Bilateral oculomotor nerve palsy as an isolated clinical finding after brainstem stroke is extremely rare. We present a case of severe bilateral fascicular oculomotor nerve palsy due to distal basilar occlusion and subsequent midbrain infarction of cardioembolic origin. The patient required mechanical aids and subsequent ptosis surgery to relieve complete ptosis at least unilaterally.

Idarucizumab administration in emergency situations: the Munich Registry of Reversal of Pradaxa® in clinical routine (MR REPAIR).

OBJECTIVES: To evaluate daily life management and functional outcome of Idarucizumab administration in case of emergency situations in patients with Dabigatran treatment. DESIGN: Multicenter observational registry study. SETTING: All hospitals with full neurological departments (n = 6) in Munich, Germany INCLUDED PATIENTS: All patients treated with Idarucizumab from 01/2016 to 03/2019. ANALYZED DATA: Indication and application of Idarucizumab, demographics and clinical parameters, and further interventions and treatments; clinical outcome was assessed with the modified Rankin scale (mRS) at 3 months after Idarucizumab administration RESULTS: Idarucizumab was administered to 32 patients for severe bleeding complications and ischemic strokes, more precisely for the following specific indications: intracranial bleeding (17 patients, 53%), ischemic stroke (8 patients, 25%), gastrointestinal bleeding (3 patients, 9%), femoral fracture, aortic dissection, and abdominal trauma and ileus (1 patient each, 3%). Additional coagulation management was performed in 7 patients (22%). Nine patients (28%) underwent emergency surgery. Seven patients (22%) received Idarucizumab before intravenous thrombolysis due to ischemic stroke and 4 of these 7 patients (13%) received mechanical thrombectomy in addition. Indication was mainly based on the history of Dabigatran intake and was irrespective of laboratory testing. At follow-up, 25% of the investigated patients had a mRS 0-2, while 25% had an unfavorable outcome (mRS 4-5). Mortality was 31%. CONCLUSION: In our study, we have shown that the administration of Idarucizumab is a rare intervention and restricted to patients with severe bleeding complications or ischemic stroke. The clinical outcome of patients who received Idarucizumab in emergency situations was poor.

[Meningism]. / Meningismus.

A thorough neurological examination in emergency situations requires the evaluation of meningeal signs. Even though in most settings, evaluation of meningism is technically not very demanding, the interpretation of findings may prove difficult. As opposed to a widely held belief, clinical signs of meningism are neither specific nor highly sensitive for detection of meningitis or subarachnoid hemorrhage. A meaningful evaluation of meningeal signs, therefore, requires careful consideration of both clinical findings and other accessory symptoms.

Myoclonic Disorders.

Few movement disorders seem to make a straightforward approach to diagnosis and treatment more difficult and frustrating than myoclonus, due to its plethora of causes and its variable classifications. Nevertheless, in recent years, exciting advances have been made in the elucidation of the pathophysiology and genetic basis of many disorders presenting with myoclonus. Here, we provide a review of all of the important types of myoclonus encountered in pediatric and adult neurology, with an emphasis on the recent developments that have led to a deeper understanding of this intriguing phenomenon. An up-to-date list of the genetic basis of all major myoclonic disorders is presented. Randomized studies are scarce in myoclonus therapy, but helpful pragmatic approaches at diagnosis as well as treatment have been recently suggested.

Neurological outcomes of antidiabetic therapy: What the neurologist should know.

Considering the causative or contributory effects of diabetes mellitus on common neurological diseases such as polyneuropathy, stroke and dementia, modern antidiabetic drugs may be expected to reduce incidence or progression of these conditions. Nevertheless, most observed benefits have been small, except in the context of therapy for diabetes mellitus type I and new-onset polyneuropathy. Recently, semaglutide, a GLP-1 analog, has been shown to significantly reduce stroke incidence in a randomized controlled trial. Beneficial effects of antidiabetic drugs on stroke severity or outcome have been controversial, though. The level of risk conferred by diabetes mellitus, the complex pathophysiology of neurological diseases, issues of trial design, side-effects of antidiabetic drugs as well as co-medication might be interacting factors that determine the performance of antidiabetic therapy with respect to neurological outcomes. It might be speculated that early treatment of prediabetes might prevent cerebral arteriosclerosis, cognitive decline or polyneuropathy more effectively, but this remains to be demonstrated.

[Clinical examination of vertigo]. / Schwindel: Neurologische Untersuchung für Nicht-Neurologen.

Acute vertigo may originate from peripheral or central vestibular disorders. As central vestibular symptoms may indicate severe brainstem or cerebellar ischemia, rapid clinical differentiation is required. To this end, evaluation of spontaneous or gaze-evoked nystagm, head-impulse test as well identification of skew deviation are most helpful.

Compressive Cervical Radiculopathy due to Vertebral Artery Dissection.

Rarely, not stroke but peripheral weakness can result from cervical artery dissection. In these cases, a mural hematoma compressing the ipsilateral C5 and/or C6 root can be demonstrated.

Prevalence of THAP1 sequence variants in German patients with primary dystonia.

Primary dystonias are a clinically and genetically heterogeneous group of movement disorders, but only for two of them, i.e., dystonia 1 and dystonia 6, the disease causing gene has been identified. Dystonia 1 is characterized by an early onset and is caused by a mutation in the TOR1A gene. Only recently, mutations in THAP1 have been shown to be the cause of DYT6 dystonia. We analyzed 610 patients with various forms of dystonia for sequence variants in the THAP1 gene by means of high resolution melting to delineate the prevalence of sequence variants and phenotypic variability. We identified seven sequence variants in patients and one sequence variant in a control. The sequence variants were not detected in 537 healthy controls. Four patients present with generalized dystonia with speech involvement of early onset, another three patients suffered exclusively from cervical dystonia of adult onset. These findings suggest that THAP1 sequence variations seem to be associated with different ages of onset and distribution of symptoms. Consequently, the phenotypic spectrum might be broader than previously assumed.

Secondary intracranial hypertension with acute intracranial pressure crisis in superficial siderosis.

Superficial siderosis of the central nervous system is a very rare disease related to hemosiderin deposits in the brain, brainstem, cerebellum and spinal cord due to chronic subarachnoid hemorrhage. Chronic increased intracranial pressure develops in about one-third of affected cases. We report a patient with superficial siderosis and sudden intracranial pressure crisis. A 29-year-old man experienced a subacute episode of headache, tinnitus and blurred vision. Magnetic resonance imaging of the brain revealed hemosiderin deposits characteristic of superficial siderosis. Extensive diagnostic work-up excluded causative pathologies of bleeding. Lumbar puncture and continuous intra-ventricular cerebrospinal fluid (CSF) pressure monitoring revealed continuous CSF pressure increase. Implantation of a ventriculo-peritoneal shunt led to complete clinical recovery. Our case emphasizes that patients with superficial siderosis may present with sudden elevation of intracranial pressure due to chronic intracranial hypertension. In this situation permanent CSF drainage provides a useful therapeutic option.

The role of the cerebellum for predictive control of grasping.

Predictive control of grasping forces when manipulating objects in the environment is suggested to reflect internal models that capture the causal relationship between actions and their consequences. The anatomical correlate of predictive control of grasping within the central nervous system is not completely understood. One structure which has been related to the neural representation of internal models is the cerebellum. Given its stereotyped cytoarchitecture, the widespread connections with cortical and subcortical sensory-motor structures and the neural activity of cerebellar Purkinje cells during sensory-motor tasks, the cerebellum has long been considered to play a major role in the establishment and maintenance of sensory-motor representations related to voluntary movement. Such representations are necessary to predict the consequences of our own movements. Here we review theoretical concepts, electrophysiological, imaging and behavioural data suggesting the cerebellum to be the anatomical and functional correlate of internal models relevant for predictive control of grasping.

CSF drainage ameliorates the motor deficit in normal pressure hydrocephalus: evidence from the analysis of grasping movements.

Apart from the classic triad of hypokinetic gait disorder, cognitive dysfunction and urinary incontinence, the clinical spectrum of normal pressure hydrocephalus has been found to affect the upper limbs. It is unclear if the motor deficit of hand and arm movements improves with CSF evacuation. The present study was designed to quantitatively assess the effect of CSF evacuation on the hypokinesia of grasping movements in normal pressure hydrocephalus. Eight subjects with normal pressure hydrocephalus grasped to lift an instrumented object prior to and following evacuation of 40 ml CSF. The build-up of fingertip forces and the kinematics of the lifting movement were slower for patients compared with healthy controls. Patients also generated excessive grasping forces when lifting and holding the object stationary prior to and following CSF evacuation. CSF evacuation significantly improved the gait disorder, the cognitive impairment and the urinary incontinence in normal pressure hydrocephalus. CSF evacuation accelerated the lifting movement and reduced the grip force overshoot. These data suggest that the measurement of grasping forces may provide an additional test to quantify the clinical response to CSF tapping in normal pressure hydrocephalus.

Acute myelopathy of unknown aetiology: a follow-up investigation.

Acute myelopathy refers to acute or subacute spinal cord dysfunction secondary to various causes. Recent studies suggest a number of distinct clinical, laboratory, MRI and outcome profiles for the various aetiologies. Nevertheless, the aetiology of acute myelopathy remains unknown in up to 60% of the patients. The probability of establishing the correct diagnosis increases with the duration of clinical and MRI follow-up. This paper presents the results of a follow-up of nine cases of acute myelopathy of unknown aetiology. One patient was lost during follow-up. Mean age of patients at the time of the follow-up interview was 48 years (+/-12). Average time from discharge to follow-up interview was 3.6 (+/-0.5) years. In four patients (mean age 45+/-13 years) the origin of acute myelopathy remained unclear after an average follow-up of 3.3 years. In one patient the diagnosis of multiple sclerosis was established during follow-up. In another patient the clinical course was suggestive for multiple sclerosis. One patient was diagnosed with systemic collagen vascular disease and in one patient a diagnosis of non-Hodgkin's lymphoma was established. It is unclear whether the patients in whom the aetiology of acute myelopathy remained unknown, even after several years of follow-up, are at a higher risk of developing progressive disease. Larger studies with longer follow-up periods and clear clinical, laboratory and MRI criteria should help to shed some light on this issue.

The clinical variability of Wallenberg's syndrome. The anatomical correlate of ipsilateral axial lateropulsion.

The dorso-lateral medullary syndrome (Wallenberg's syndrome) is produced by infarction of a wedge of lateral medulla posterior to the inferior olivary nucleus and is usually caused by vertebral artery occlusion. Ipsilateral axial lateropulsion as an initial symptom of vertebral artery occlusion is rather rare and the anatomical structure responsible is still uncertain. Here we describe two patients presenting with ipsilateral axial lateropulsion as an initial symptom of vertebral artery occlusion. In one the stroke affected the dorso-lateral aspect of the medulla, in the other more lateral aspects of the medulla were involved. Our data suggest that ipsilateral axial lateropulsion may be caused by lesions of different topography involving either the vestibular nuclei, the cerebellar peduncle or the spinocerebellar tracts.

Sensory timing cues improve akinesia of grasping movements in Parkinson's disease: a comparison to the effects of subthalamic nucleus stimulation.

Five parkinsonian subjects with chronic bilateral stimulation of the subthalamic nucleus and five sex- and age-matched healthy controls grasped, lifted, and held an instrumented object. The grip-lift task was either performed at self-determined speed or in response to an auditory cuing signal. Parkinsonian subjects performed the task with subthalamic nucleus stimulation switched ON and OFF. In Parkinson's disease, stimulation of the subthalamic nucleus and the presentation of auditory timing cues improved akinesia of both the grasp and lift components of the task. The finding that auditory timing cues improve akinesia in the absence of subthalamic nucleus stimulation suggests that the basal ganglia are less involved in the control of movements made in response to environmental cues. However, subthalamic nucleus stimulation caused parkinsonian subjects to apply excessive grip forces, regardless of whether the movement was made under self-determined or externally guided speed conditions. This implies that subthalamic nucleus stimulation produces a generalized upregulation in the gain of all components of a movement without the subtlety of focused control that is required to normalize performance.

Broadening a classic clinical triad: The hypokinetic motor disorder of normal pressure hydrocephalus also affects the hand.

The clinical spectrum of normal pressure hydrocephalus is thought to comprise the triad of hypokinetic gait disorder, dementia and urinary incontinence. In contrast, motor abnormalities involving the upper limbs in normal pressure hydrocephalus have not yet received a great deal of attention. The present study was designed to quantitatively assess grasping movements in normal pressure hydrocephalus and to compare the performance with that in Parkinson's disease. Eight subjects with normal pressure hydrocephalus, eight subjects with Parkinson's disease and eight healthy control subjects grasped to lift an instrumented object. The built-up of fingertip forces during the early phase and the kinematics of the lifting movement during the late phase of the grip-lift synergy were slower for patients compared to healthy controls. Patients generated abnormally high fingertip forces when lifting and holding the object stationary. The slowness of the grip-lift synergy and the force overshoot was similar for both patient groups. Our data demonstrate that the hypokinetic motor deficit in normal pressure hydrocephalus also involves the hand, and that the pattern of deficits shares several features of those found in Parkinson's disease.

Diagnostic relevance of transcranial magnetic and electric stimulation of the facial nerve in the management of facial palsy.

OBJECTIVE: Earlier investigations have suggested that isolated conduction block of the facial nerve to transcranial magnetic stimulation early in the disorder represents a very sensitive and potentially specific finding in Bell's palsy differentiating the disease from other etiologies. METHODS: Stimulation of the facial nerve was performed electrically at the stylomastoid foramen and magnetically at the labyrinthine segment of the Fallopian channel within 3 days from symptom onset in 65 patients with Bell's palsy, five patients with Zoster oticus, one patient with neuroborreliosis and one patient with nuclear facial nerve palsy due to multiple sclerosis. RESULTS: Absence or decreased amplitudes of muscle responses to early transcranial magnetic stimulation was not specific for Bell's palsy, but also evident in all cases of Zoster oticus and in the case of neuroborreliosis. Amplitudes of electrically evoked muscle responses were more markedly reduced in Zoster oticus as compared to Bell's palsy, most likely due to a more severe degree of axonal degeneration. The degree of amplitude reduction of the muscle response to electrical stimulation reliably correlated with the severity of facial palsy. CONCLUSIONS: Transcranial magnetic stimulation in the early diagnosis of Bell's palsy is less specific than previously thought. While not specific with respect to the etiology of facial palsy, transcranial magnetic stimulation seems capable of localizing the site of lesion within the Fallopian channel. SIGNIFICANCE: Combined with transcranial magnetic stimulation, early electrical stimulation of the facial nerve at the stylomastoid foramen may help to establish correct diagnosis and prognosis.

The beneficial effects of subthalamic nucleus stimulation on manipulative finger force control in Parkinson's disease.

We investigated the differential effects of levodopa medication and STN stimulation on finger force control in Parkinson subjects grasping to lift an object and performing vertical point-to-point movements of a hand-held object. The experiments were conducted in four treatment conditions: off-drug/off-stimulation, off-drug/on-stimulation, on-drug/off-stimulation and on-drug/on-stimulation. We found that the bradykinesia in Parkinsonian subjects improved by both levodopa medication and STN stimulation. As compared to healthy subjects, excessive grip force was observed in all Parkinson subjects, regardless of the treatment condition. This force excess was most pronounced in the on-drug condition and ameliorated by STN stimulation. We observed reliable correlations between the amount of force overflow and the severity of levodopa-induced dyskinesias in the on-drug condition. Despite some similarities regarding therapeutic effects on bradykinesia, our findings contrast with earlier observations with respect to the differential effects of levodopa and STN stimulation on the scaling of fingertip forces in Parkinson's disease. While levodopa causes an overshoot of fingertip forces, STN stimulation appears to be sufficient to alleviate, but not normalise the force excess. STN stimulation enables Parkinson subjects to scale grip force more accurately to the loads arising from voluntary manipulation of hand-held objects.