[Laboratory diagnostics in transient loss of consciousness : Serum lactate compared to serum creatine kinase as diagnostic indicator for generalized tonic-clonic seizures]. / Labordiagnostik bei transienten Bewusstseinsstörungen : Serumlaktatwert im Vergleich zur Serumkreatinkinase als diagnostischer Indikator für generalisierte tonisch-klonische Anfälle.

BACKGROUND: Laboratory parameters can help in the differential diagnostics of acute episodes of transient loss of consciousness. Especially serum lactate and serum creatine kinase (CK) levels may provide valuable hints to distinguish generalized tonic-clonic seizures (GTCS) from syncope. MATERIAL AND METHODS: Serum lactate levels at admission and CK levels 10-48 h after the episodes that led to admission were compared between patients with GTCS (n = 30) and those with syncope (n = 15). In addition, sensitivity and specificity of lactate and CK as diagnostic markers for syncope and GTCS were determined. RESULTS: The serum lactate and serum CK levels were significantly increased in patients with GTCS as compared to syncope patients (serum lactate: p < 0.001; CK: p < 0.005). The area under the curve (AUC) for serum lactate as an indicator for GTCS was 0.94 (95% confidence interval [CI] 0.88-1.0). For CK the receiver operating characteristics (ROC) analysis produced an AUC of only 0.77 (95% CI: 0.63-0.9). CONCLUSION: The determination of the lactate value as point-of-care diagnostics appears to be highly relevant in the rapid clarification of unclear episodes with transient loss of consciousness. The CK level at follow-up is also suitable for distinguishing GTCS from syncope but is inferior to the serum lactate value.

[Mycoplasma Pneumoniae-Induced Meningoencephalitis]. / Mykoplasma-pneumoniae-assoziierte Meningoenzephalitis.

In clinical practice, secondary infections of the central nervous system (CNS) represent rare yet severe complications of their respective primary infections. In this case report, we describe a 22-year-old patient with a medical history of Asthma bronchiale, who developed significant neurological deficits after a respiratory infection. The neurological symptoms progressed despite antibiotic therapy with vancomycin, ampicillin and ceftriaxone. The patient's cerebrospinal fluid and a cranial magnetic resonance imaging (MRI) furnished evidence of acute meningoencephalitis. Microbiological assessment confirmed an acute mycoplasma pneumonia infection. Changing the patient's antibiotic regimen to minocycline and prednisolone led to significant clinical improvement. Pathomechanisms and therapeutic options to treat meningoencephalitis will be discussed in the following.

[Drug-induced seizures]. / Medikamentös induzierte epileptische Anfälle.

Drug-induced seizures are in view of a constantly ageing population and increasingly frequent polypharmacotherapy an increasing problem in daily routine praxis. Identification of potentially seizure-inducing drugs may help generating risk profiles for individual patients. Drug-induced seizures have often been seen as a complication of psychopharmacological therapy, but its occurrence has also been described in response to a great diversity of compounds such as antibiotics, sympathomimetics and anaesthetics. The present article outlines a synopsis of the most prevalent seizure-inducing drugs as well as strategies how to deal with a patient suffering from a drug-induced seizure.

[The 'red puffy ear sign'--a clinical sign to diagnose a rare cause of meningoencephalitis]. / Das "red puffy ear sign" - ein klinisches Zeichen zur Diagnose einer seltenen Meningoenzephalitis.

We report on the case of a 63-year-old patient with a meningoencephalitis, presenting itself with headache and a general neuropsychological retardation. Additionally, a reddening and swelling of both auricles could be seen. Magnetic resonance imaging showed confluent, contrast-uptaking lesions. In the cerebrospinal fluid an aseptic lymphocytic pleocytosis was found. A biopsy of the ear revealed a chronic lymphoplasmacellular inflammatory reaction. We diagnosed a relapsing polychrondritis, an inflammatory disease of the cartilage, which can in rare cases affect the central nervous system. Typically, the patients complain about red swollen ears, the "red puffy ear sign". After initiation of steroid and azathioprin therapy the patient recovered fully.

[Drug-induced tremor]. / Medikamentös-induzierter Tremor.

Drug-induced tremor is an important differential diagnosis for tremor syndromes. In view of a constantly ageing population and increasingly frequent polypharmacotherapy, identification of potentially tremor-inducing drugs may help generating risk profiles for individual patients. Drug-induced tremor has often been seen as a complication of antipsychotic therapy, but its occurrence has also been described in response to a great diversity of compounds such as antidepressants, sympathomimetics, antiarrhythmics, antiepileptics and other drugs. The present article presents a synopsis of the most prevalent tremor-inducing drugs as well as strategies to overcome drug-induced tremor, either by replacement of the causative drug or by symptomatic therapies.

[Bilateral wrist drop - central or peripheral lesion?]. / Bilaterale Fallhand - Zentrale oder Periphere Läsion?

The wrist drop, also called carpoptosis or drop hand, is a common clinical presentation in case of peripheral damage to the radial nerve. But what about the picture of a bilateral finger/wrist drop?! We report the case of a 61-year-old female patient who was admitted to the hospital for myocardial infarction. Subsequently she developed a right dominant bilateral wrist drop. Further neurological examination revealed a positive Wartenberg sign pointing towards a central motoric dysfunction. The following native cerebral CT scan demonstrated bilateral hypodense lesions in both hand knobs in the precentral gyri. Subsequent MRI confirmed acute cerebral infarction in these two but also several other, clinically silent, locations. Further diagnostic work-up revealed a hypokinetic cardiac apex suggesting cardiac embolism to be the cause for cerebral thrombembolism and the clinically leading symptom of right-dominant bilateral finger/wrist drop. Besides the case presentation also the differential diagnosis and clinical test for diagnostic work-up of wrist drops are presented and discussed.

[Transcranial magnetic stimulation for psychogenic tremor - a pilot study]. / Der Einsatz der transkraniellen Magnetstimulation beim psychogenen Tremor - eine Pilotstudie.

Psychogenic tremor is the most common psychogenic movement disorder. Its prognosis is widely held to be poor and strongly depends on the patient's insight into the psychogenicity of the syndrome. The clinical value of transcranial magnetic stimulation (TMS) for (i) establishing the diagnosis with a high level of certainty, (ii) modulating symptom severity and (iii) facilitating patients' insight into psychogenicity was tested in 11 patients with psychogenic tremor of the upper limb. After explaining the psychogenic origin of the syndrome and providing a neurobiological model, 30 TMS pulses were applied over the hand area of the primary motor cortex contralateral to the affected hand(s) at a rate of 0.2 Hz. 15 pulses were administered at intensities of 120 % and 140 % of the resting motor threshold, respectively. Kinematic motion analysis was used to document the effectiveness of the TMS procedure. All patients met the diagnostic criteria of conversion disorder. Time elapsed since symptom onset was on average 48 to 57 months. Tremor affected both hands in 8 patients, one patient had additional head tremor. The TMS procedure caused a significant reduction of tremor frequency and thus established the diagnosis of documented psychogenic tremor according to the criteria proposed by Fahn and Williams (1988) in each patient. The duration of symptom relief was transient in 7 patients, 4 patients had lasting symptom relief. The present pilot study demonstrates that TMS is a helpful tool to (i) establish the diagnosis of psychogenic hand tremor with a high level of certainty, (ii) reduce tremor intensity and (iii) facilitate the patient's insight into the psychogenic origin of the syndrome as a prerequisite to obtain adherence to psychotherapy.

Treatment strategy and long-term outcome in patients with deep lumbosacral arteriovenous fistulas. A single center analysis in nineteen patients.

OBJECTIVE: Deep lumbosacral dural arteriovenous fistulas (lsDAVF) are rare and present serious diagnostic and treatment difficulties. In our current analysis we present our treatment strategy and the long-term clinical outcome of nineteen patients with lsDAVF. PATIENTS AND METHODS: We retrospectively analyzed our radiological and medical records for patients presenting with SDAVF between 1990 and 2018 at the University Hospital Aachen. We identified twenty patients with a lsDAVF. All patients were treated surgically. One patient died of pulmonary embolism three months after treatment and was excluded from our outcome analysis. Clinical data at time of admission, discharge, one year after discharge and at the last follow-up were evaluated according to modified Aminoff-Logue disability score (AL-score) for this analysis. RESULTS: Mean age was 65 ±â€¯7 years (median, 67; range, 53-78), sixteen patients (84 %) were male. After surgery, four patients developed a recurrent fistula in the same shunt zone and were re-treated microsurgically. Follow-up data one year after treatment was available in 15 patients. No relevant changes in AL-score were observed within this period. For the long-term follow-up analysis, data of 13 patients were available; 38.5 % of patients developed late functional deterioration. CONCLUSION: In our cohort, patients with deep lumbosacral dural arteriovenous fistula had a higher risk of early recurrence compared to patients with thoracolumbar SDAVF, with a considerable percentage of late functional deterioration. Thus strict clinical and radiologic long-term follow-up examinations are recommended in those patients.

Long-Term Outcome of Patients with Spinal Dural Arteriovenous Fistula: The Dilemma of Delayed Diagnosis.

BACKGROUND AND PURPOSE: The impact of various radiologic and clinical features on the long-term outcome in spinal dural arteriovenous fistulas is still unclear; thus, they are the purpose of this study. MATERIALS AND METHODS: We retrospectively analyzed our medical data base for all patients treated for spinal dural arteriovenous fistula in our institution between 2006 and 2016. Patient age, neurologic status at the time of diagnosis, the duration of symptoms from onset to diagnosis, and follow-up information were evaluated. The extent of medullary T2WI hyperintensity, intramedullary contrast enhancement, and elongation of perimedullary veins on MR imaging at the time of diagnosis were additionally analyzed. RESULTS: Data for long-term outcome analysis were available in 40 patients with a mean follow-up of 52 months (median, 50.5 months; range, 3-159 months). The mean age at the time of diagnosis was 69.27 ± 9 years (median, 71 years; range, 53-84 years) with a male predominance (n = 32; 80%). The mean duration of symptoms was 20.2 months (median, 10 months; range, 1-120 months). Shorter duration of symptoms at the time of diagnosis was significantly correlated with better outcome of symptoms (P < .05). CONCLUSIONS: Spinal dural arteriovenous fistulas are characterized by interindividually variable clinical presentations, which make a determination of specific predictors for long-term outcome more difficult. Fast and sufficient diagnosis might result in a better outcome after treatment. The diagnosis of spinal dural arteriovenous fistula remains markedly delayed, reflecting an ongoing lack of knowledge and awareness among treating physicians of this rare-but-serious disease.

Electrical somatosensory stimulation improves movement kinematics of the affected hand following stroke.

AIM: The effect of electrical somatosensory stimulation on motor performance of the affected hand was investigated in 12 chronic subcortical stroke subjects. METHODS: Subjects performed index finger and hand tapping movements as well as reach-to-grasp movements with both the affected and unaffected hand prior to (baseline conditions) and following (1) 2 h of electrical somatosensory stimulation (trains of five pulses at 10 Hz with 1 ms duration delivered at 1 Hz with an intensity on average 60% above the individual somatosensory threshold) of the median nerve of the affected hand or (2) 2 h of idle time on separate occasions at least 1 week apart. The order of sessions was counterbalanced across subjects. RESULTS: Somatosensory stimulation of the median nerve of the affected hand, but not a period of idle time, enhanced the frequency of index finger and hand tapping movements and improved the kinematics of reach-to-grasp movements performed with the affected hand, compared with baseline. Somatosensory stimulation did not impact on motor performance of the unaffected hand. DISCUSSION: The data suggest that electrical somatosensory stimulation may improve motor function of the affected hand after stroke; however, further studies are needed to test if the implementation of somatosensory stimulation in rehabilitation of hand function also impacts on manual activities of daily life after stroke.

The discriminative value of blood gas analysis parameters in the differential diagnosis of transient disorders of consciousness.

AIM: The differentiation between epileptic and non-epileptic episodes can be challenging. Our aim was to compare lactate, anion gap (AG), bicarbonate and the Denver Seizure Score (DSS) as point-of-care test (POCT) markers for episodes of transient alterations of consciousness. METHODS: The blood serum parameters were drawn at arrival in the emergency department (ED) within 2 h of the episode. After calculating AG and DSS values, the four parameters were compared retrospectively between patients with generalized tonic-clonic seizures (GTCS) (n = 165) and patients with other disorders of consciousness [syncopes (n = 43), and psychogenic non-epileptic seizures (n = 15)]. Additionally, we compared all values among men and women. RESULTS: In GTCS patients, all four parameters differed significantly compared to non-epileptic episode patients (p < 0.001). Serum lactate showed significant additional benefit over the remaining values, with an AUC of 0.947 (95% CI 0.92-0.975) and a high sensitivity and specificity for an optimal cut-off value of 2.45 mmol/l. For DSS, the AUC was 0.857 (95% CI 0.808-0.906; cut-off: 0.35), and for AG 0.836 (95% CI 0.783-0.889; cut-off: 12.45 mmol/l). In the case of serum bicarbonate, the AUC was 0.831 (95% CI 0.775-0.886; cut-off: 22.75 mmol/l). In the sex-dependent comparison, the results were similar. Men showed more significant differences in the compared values than women. CONCLUSIONS: Serum lactate is best suited as POCT marker in the differential diagnosis of epileptic and non-epileptic episodes and is superior to AG, DSS and bicarbonate. The differences among sexes may pose a challenge in their implementation and interpretation.

Spinal Epidural Arteriovenous Fistula with Perimedullary Venous Reflux: Clinical and Neuroradiologic Features of an Underestimated Vascular Disorder.

BACKGROUND AND PURPOSE: The purpose of this study was to discuss the clinical and radiologic characteristics of spinal epidural arteriovenous fistulas (SEAVF) and demonstrate their specific angiomorphology in a single-center series. MATERIALS AND METHODS: Thirteen consecutive patients were diagnosed with SEAVF at RWTH Aachen University Hospital between 2006 and 2018 and were included in this study. All patients had MR imaging and DSA before treatment; 10 of these 13 patients received contrast-enhanced MRA (CE-MRA). RESULTS: The mean patient age was 72 ± 8 years. Paraparesis was present in 12 (92%) patients. Sphincter dysfunction and sensory symptoms were observed in 7 (54%) and 6 (46%) patients, respectively. The mean duration of symptoms was 6 ± 8 months. Congestive myelopathy on MR imaging was present in all patients. Prominent arterialized perimedullary veins were demonstrated in only 3 cases. CE-MRA revealed arterialized perimedullary veins and an arterialized epidural pouch in 9/10 (90%) patients, mostly located ventrolaterally. DSA demonstrated a multisegmental extension of the arterialized ventrolateral epidural pouch in 6 (46%) cases. An intradural radicular drainage vein was localized distant from the original fistula point in 3 (23%) patients. CONCLUSIONS: Congestive myelopathy with an acute/subacute clinical course was the dominant finding in spinal epidural arteriovenous fistulas. CE-MRA is a powerful diagnostic tool for identifying arterialized perimedullary veins as well as an arterialized epidural pouch. While arterialized perimedullary veins frequently present with only mild enlargement and elongation in spinal epidural arteriovenous fistulas, the arterialized epidural pouch is frequently located ventrolaterally and may extend over several vertebral levels. DSA remains the criterion standard to precisely visualize a spinal epidural arteriovenous fistula and its intradural radicular drainage vein, which may be located distant from the fistulous point.

Clinical and Radiologic Characteristics of Deep Lumbosacral Dural Arteriovenous Fistulas.

BACKGROUND AND PURPOSE: Spinal dural arteriovenous fistulas located in the deep lumbosacral region are rare and the most difficult to diagnose among spinal dural arteriovenous fistulas located elsewhere in the spinal dura. Specific clinical and radiologic features of these fistulas are still inadequately reported and are the subject of this study. MATERIALS AND METHODS: We retrospectively evaluated all data of patients with spinal dural arteriovenous fistulas treated and/or diagnosed in our institution between 1990 and 2017. Twenty patients with deep lumbosacral spinal dural arteriovenous fistulas were included in this study. RESULTS: The most common neurologic findings at the time of admission were paraparesis (85%), sphincter dysfunction (70%), and sensory disturbances (20%). Medullary T2 hyperintensity and contrast enhancement were present in most cases. The filum vein and/or lumbar veins were dilated in 19/20 (95%) patients. Time-resolved contrast-enhanced dynamic MRA indicated a spinal dural arteriovenous fistula at or below the L5 vertebral level in 7/8 (88%) patients who received time-resolved contrast-enhanced dynamic MRA before DSA. A bilateral arterial supply of the fistula was detected via DSA in 5 (25%) patients. CONCLUSIONS: Clinical symptoms caused by deep lumbosacral spinal dural arteriovenous fistulas are comparable with those of spinal dural arteriovenous fistulas at other locations. Medullary congestion in association with an enlargement of the filum vein or other lumbar radicular veins is a characteristic finding in these patients. Spinal time-resolved contrast-enhanced dynamic MRA facilitates the detection of the drainage vein and helps to localize deep lumbosacral-located fistulas with a high sensitivity before DSA. Definite detection of these fistulas remains challenging and requires sufficient visualization of the fistula-supplying arteries and draining veins by conventional spinal angiography.

Lactate as a diagnostic marker in transient loss of consciousness.

PURPOSE: The diagnostic classification of disorders of consciousness is often challenging, particularly the distinction between epileptic and non-epileptic seizures. The aim of the study was to examine serum lactate as a diagnostic marker of transient loss of consciousness. METHOD: Serum lactate levels in blood samples drawn within 2h of the event were compared retrospectively between patients with generalized tonic-clonic seizures (n=195) and patients with other seizures (syncopes [n=52], psychogenic non-epileptic seizures [n=17], and complex focal seizures [n=37]), respectively. RESULTS: Serum lactate in patients with generalized tonic-clonic seizures was significantly (p<0.001, Mann-Whitney-U test) increased in comparison to other forms of seizure incidences. The area under the ROC-curve was 0.94 (95% CI 0.91-0.96). For a cut-off concentration of 2.45mmol/l, the sensitivity was 0.88 and the specificity 0.87. CONCLUSIONS: Serum lactate levels in the acute diagnosis were an excellent biomarker for the discrimination of generalized seizures from psychogenic non-epileptic and syncopal events, corroborating its importance for the standard work-up of acute disturbances of consciousness.

Use of cryostat sections from snap-frozen nervous tissue for combining stereological estimates with histological, cellular, or molecular analyses on adjacent sections.

Adequate tissue preparation is essential for both modern stereological and immunohistochemical investigations. However, combining these methodologies in a single study presents a number of obstacles pertaining to optimal histological preparation. Tissue shrinkage and loss of nuclei/nucleoli from the unprotected section surfaces of unembedded tissue used for immunohistochemistry may be problematic with regard to adequate stereological design. In this study, frozen cryostat sections from hippocampal and cerebellar regions of two rat strains and cerebellar and cerebral regions from a human brain were analyzed to determine the potential impact of these factors on estimates of neuron number obtained using the optical disector. Neuronal nuclei and nucleoli were clearly present in thin sections of snap-frozen rat (3 microm) and human (6 microm) tissue, indicating that neuronal nuclei/nucleoli are not unavoidably lost from unprotected section surfaces of unembedded tissue. In order to quantify the potential impact of any nuclear loss, optical fractionator estimates of rat hippocampal pyramidal cells in areas CA1-3 and cerebellar granule and Purkinje cells were made using minimal (1 microm) upper guard zones. Estimates did not differ from data reported previously in the literature. This data indicates that cryostat sections of snap-frozen nervous tissue may successfully be used for estimating total neuronal numbers using optical disectors.

Neuron loss during early adulthood following prenatal low-dose X-irradiation in the mouse brain.

PURPOSE: Apart from subsequent cell death, little is known about long-term effects of a prenatal low-dose X-irradiation (PLDI) on nuclear (n) and mitochondrial (mt) DNA, and whether these effects are connected with reduced neuron numbers in the adult brain. MATERIALS AND METHODS: Pregnant mice were X-irradiated with 0, 10 or 50cGy at day 13 (E13) of pregnancy. One day after (E14), or postnatally at day 25 (P25) or P180, the brains of the offspring were analysed concerning the extent of nDNA repair, mt biogenesis, and the relative content of nDNA single strand breaks (SSB). Stereology was applied for evaluating neuronal loss. RESULTS: One day after irradiation no unrepaired SSB were detected. Significant results were mainly obtained for hippocampal pyramidal cells at P180, particularly cell loss following 50 cGy PLDI, increased SSB content and mt biogenesis (0 vs. 10cGy) but decreased mt biogenesis for 10 vs. 50 cGy. CONCLUSIONS: A hypothesis closely related to that regarding molecular events during aging is presented for explaining this second wave of cell death in adult mice following PLDI as a result of accumulated mtDNA damage caused by PLDI. A possible relation to the neurodegenerative hypothesis of schizophrenia is discussed.