[Long-term outcome of macular neovascularization secondary to choroidal osteoma with and without intravitreal anti-VEGF(vascular endothelial growth factor)- treatment]. / Langzeitverlauf von makulären Neovaskularisationen bei chorioidalen Osteomen mit und ohne intravitreale Anti-VEGF(vascular endothelial growth factor)-Therapie.

BACKGROUND: Choroidal osteoma (CO) is a benign ossifying ocular tumor, which is unilateral in most cases. The CO may cause severe visual impairment, especially in the case of a secondary macular neovascularization (MNV). OBJECTIVE: Based on a case series of patients with MNV secondary to CO, the variability of the clinical course with and without intravitreal anti-vascular endothelial growth factor (VEGF) treatment is presented. METHODS: All patients diagnosed with secondary MNV due to CO between 2007 and 2023 were retrospectively assessed with respect to the clinical course. RESULTS: In this study 7 eyes of 5 patients (4 women, 1 man) were diagnosed with secondary MNV due to CO. Intravitreal anti-VEGF treatment was carried out in 2 patients with unilateral MNV and 1 patient was treated in both eyes for bilateral MNV. In another case with bilateral MNV, only 1 eye was treated because of fibrosis in the other eye. A further case with unilateral CO and MNV scars at the initial diagnosis was left untreated. Overall, in 3 out of 5 eyes treated with intravitreal VEGF inhibition stabilization or improvement of visual acuity could be achieved. CONCLUSION: In our case series intravitreal anti-VEGF treatment attained a functional stabilization or improvement in 3 out of 5 treated eyes. In one case of CO-associated MNV fibrosis rapidly developed without treatment. Therefore, the clarification for patients with CO about the lifelong risk for development of a secondary MNV is essential in individual cases for early treatment. As no standardized treatment scheme for intravitreal VEGF antibodies for CO-related MNV exists, the treatment is planned on an individual basis.

Practical management of new oral anticoagulants after total hip or total knee arthroplasty.

Within the past 5 years, the oral anticoagulants rivaroxaban, apixaban, and dabigatran etexilate have been approved for the prevention of venous thromboembolism in adult patients after elective hip or knee arthroplasty in the European Union and many other countries worldwide. These agents differ from the previously available anticoagulants because they selectively and directly inhibit a single factor in the coagulation cascade-rivaroxaban and apixaban inhibit Factor Xa, and dabigatran inhibits Factor IIa (thrombin)-potentially enhancing the predictability of their anticoagulant effect. Currently, although some guidelines provide recommendations for the use of rivaroxaban, dabigatran etexilate, and apixaban in clinical practice, there are still questions regarding the optimal practical management of patients receiving these agents. This article briefly reviews the practical limitations associated with conventional anticoagulants, discusses potential issues with the practical management of the newer oral anticoagulants, and provides clinical experience from a single institution where rivaroxaban and dabigatran etexilate have been used within their approved indications.

Recurrent Miller Fisher syndrome: clinical and laboratory features.

To present two patients with Miller Fisher syndrome (MFS) recurrence after 35 and 44 years and review of the literature on recurring MFS. All identified cases with recurrent MFS were evaluated. Age, gender, clinical features of first and recurrent MFS, course of disease, laboratory findings, therapy and outcome were transformed into tables. Twenty-eight patients (16 men, 12 women; mean age at the first episode 34 years (range 13-57 years); mean age at the latest episode 47 years (range 21-66 years) with a total of 70 MFS episodes were identified. Twenty-one patients had a single recurrence, five patients had two recurrences, one patient had four recurrences and one patient had seven recurrences. The mean interval between attacks was 9.45 years (3 months to 44 years). In 76% of the initial episodes and in 81% of the recurrent episodes, an infectious disease preceded MFS. Additional facial and bulbar symptoms and autonomic disturbances were frequent findings. Cerebrospinal fluid (CSF) and electrodiagnostic findings were unspecific. If tested, autoantibodies against GQ1b had been positive in all episodes. In about half of the patients, immunotherapy was applied. The outcome was favourable in most patients. Recurrence of MFS is a rare quite uniform condition with a mostly favourable prognosis.

Neurological complications in Fabry disease.

In Fabry disease, deficiency of α-galactosidase A results in the accumulation of glycosphingolipids in body fluids and tissues including corneas, blood vessels, kidneys and also structures of the central and peripheral nervous system. Many patients show cardiovascular and cerebrovascular dysfunction. Cerebrovascular dysfunction is particularly associated with a high risk of strokes and of mortality even at a young age. The prevalence and severity of cerebrovascular complications increase with patients'age. Clinical data as well as histologic and neurophysiologic studies showed predominantly small fiber dysfunction in patients with Fabry disease. We recently performed quantitative sensory testing in patients with Fabry disease and found reduced cold and heat-pain detection thresholds, while nerve conduction velocities were only mildly reduced. From our findings, we concluded that small fiber dysfunction is more prominent than large fiber dysfunction in Fabry patients. Clinically, small fiber dysfunction contributes to recurrent episodes of burning and lancinating pain and paresthesias in the distal extremities. Such episodes can be typically triggered by changes of the environmental temperature, particularly by warming. Moreover, dysfunction of small thinly-myelinated and unmyelianated nerve fibers accounts for altered sympathetic and parasympathetic modulation. Sympathetic dysfunction explains the hypohidrosis and a subsequent poor exercise and heat tolerance. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase A is available. We could demonstrate improvement of small fiber neuropathy and neuropathic pain after 18-23 months of ERT, which probably resulted from glycosphingolipid clearing from perineurial cells, axons and Schwann cells or from blood vessels supplying the nerves.

Smell and taste disorders in polyneuropathy: a prospective study of chemosensory disorders.

OBJECTIVE: The aim of the study was to assess the occurrence and the frequency of chemosensory dysfunction in patients with polyneuropathy (PNP). METHODS: We performed a prospective observational study. Olfactory function was assessed using the standardized 'Sniffin' Sticks' test to measure odor threshold for phenyl ethyl alcohol, odor discrimination, and odor identification. Gustatory function was assessed using the standardized 'taste strips' test. In addition, we assessed etiology, neurophysiology, and severity of the PNP, and the patients' comorbidities and medication. RESULTS: A total of 53 consecutive patients were enrolled (15 women, 38 men; mean age 61 years); 27 of them (51%) exhibited olfactory dysfunction and 23 of them (43%) gustatory dysfunction. Patients with diabetic PNP had significantly lower taste scores than patients with inflammatory, genetic, or idiopathic PNP. In addition, odor identification was negatively correlated with PNP severity. CONCLUSION: The applied bedside tests are useful to detect chemosensory dysfunction in patients with PNP. Chemosensory dysfunction is quite frequent in these patients.

Relation between ictal asystole and cardiac sympathetic dysfunction shown by MIBG-SPECT.

OBJECTIVE: Tachyarrhythmias are common during epileptic seizures while bradyarrhythmias or asystoles are less frequent. Ictal asystole might be related to epilepsy-induced cardiac sympathetic denervation. METHODS: To evaluate cardiac post-ganglionic denervation in epilepsy patients with ictal asystoles we assessed I123-meta-iodobenzylguanidine (MIBG) as a marker of post-ganglionic cardiac norepinephrine-uptake, using single photon emission computed tomography (MIBG-SPECT). RESULTS: In five of 844 patients with presurgical video-electroencephalography-monitoring, we recorded ictal asystoles during nine of 37 seizures. Asystole patients underwent cardiologic examination (Holter-electrocardiogram, echocardiogram) and cardiac MIBG-SPECT. We compared cardiac MIBG uptake in the asystole patients to the uptake in 18 temporal lobe epilepsy (TLE) patients without bradyarrhythmias and in 14 controls without cardiac or neurological disease. As the cardiological examinations were unremarkable in all subjects, the heart/mediastinum-MIBG-uptake ratios (H/M-ratios) differed significantly between the three groups (P = 0.004). H/M-ratios were lower in asystole TLE patients (mean +/- SD: 1.58 +/- 0.3) than in patients without asystole (1.81 +/- 0.18; P = 0.037) or controls (1.96 +/- 0.16). CONCLUSIONS: Pronounced reduction in cardiac MIBG uptake of asystole patients indicates post-ganglionic cardiac catecholamine disturbance. Impaired sympathetic cardiac innervation limits adjustment and heart rate modulation, and may increase the risk of asystole and ultimately sudden unexpected death in epilepsy (SUDEP).

Effects of peer-assisted training during the neurology clerkship: a randomized controlled study.

OBJECTIVE: To determine the efficacy of peer-assisted clinical skills training for students during their neurology clerkship. METHODS: Students (n = 122) were randomized to get clinical skills training from either student (peer) instructors (experimental group) or from experienced clinical staff (control group). The remaining schedule during the clerkship did not differ between both groups. Primary endpoint was students' practical skills and knowledge tested at the end of the course by a written test and objective structured clinical examination (OSCE). Secondary endpoints were evaluation of the practical training and self-estimated gain in theoretical and practical competence. RESULTS: In the written test, the peer-trained group (n = 66) scored 69.5 +/- 10.2 (95% CI 67-72) points of 100 and the postgraduates-trained group (n = 56) 66.7 +/- 11.4 (95% CI 63.6-69.8) (P = 0.15). In the OSCE the peer-trained group scored 93.7 +/- 6.3 (95% CI 92.1 to 95.2) points of 100 and the postgraduates-trained group 92 +/- 5.1 (95% CI 90.6 to 93.4) (P = 0.11). In the evaluation and self-assessment items, there was no significant difference between the two groups except for the postgraduates' higher competence (P = 0.004). CONCLUSION: Peer-trained students pass written exam and OSCE as efficient as postgraduates-trained students. Self-assessed learning success is equally rated in both groups.

[The Erlangen examination. An alternative to multiple choice testing for German neurology students]. / ERlanger Neurologisches Examen-STrukturiert (ERNEST). Alternative zur Multiple-Choice-Prüfung zum Abschluss des Blockpraktikums Neurologie.

BACKGROUND: With the latest revision of the German Medical Licensing Regulation in 2002, educating faculties gained more freedom in the organisation and assessment of trainees. The Erlangen Neurological Exam Structured (ERNEST) is an alternative for assessing competency in clinical knowledge at the end of the neurological general education. The answers must be given in written, short essay format. METHOD: The students (mostly 5th year of medical education) underwent the ERNEST including eight sections with ten to 15 questions each and the MC examination as had been applied earlier. The results were given in percentage scores. The examination was evaluated by a questionnaire using Likert scales. RESULTS: A total of 128 students (81 women, 47 men) with a mean age of 25.3 years (range 22-33) completed their initial training by the exam. The mean score was 69.6% in the ERNEST and 73.4% in the MC part (P<0.001). Of the students 12.5% in ERNEST and 11.7% in the MC (nonsignificant) failed to reach the projected score of 60% to pass the exam. Correlation between the ERNEST and MC results was significant, with r=0.784 (Pearson's coefficient, P<0.001). The students evaluated the aspects innovation, length, format, clarity of the tasks, closeness to reality, and compatibility with general physician's practice as predominantly positive. CONCLUSION: The ERNEST is a viable alternative form of assessment as compared to the conventional MC exam. The basic quantitative parameters of the assessment comply with the requirements of medical assessments. The students evaluated ERNEST as mainly positive.

Cardiovascular autonomic function in poststroke patients.

BACKGROUND: Autonomic dysregulation is frequent in acute ischemic stroke. Several studies concluded that imbalance between sympathetic and parasympathetic cardiovascular function predisposes to malignant cardiac arrhythmia. However, there are few data on cardiovascular autonomic function in post-acute stroke patients. OBJECTIVE: To study cardiovascular autonomic function 18 to 43 months after lacunar stroke. PATIENTS AND METHODS: We continuously monitored R-R intervals (RR(int)), mean blood pressure (BP(mean)), and respiration in 15 patients (8 women, aged 43 to 73 years) after right-sided stroke, in 13 patients (7 women, aged 50 to 75 years) after left-sided stroke, and in 21 age- and sex-matched controls at rest. We used autoregressive spectral analysis to assess sympathetic and parasympathetic modulation as powers of RR(int) and BP(mean) oscillations in the low-frequency (LF: 0.04 to 0.15 Hz) and high-frequency bands (HF: 0.15 to 0.5 Hz). RESULTS: Mean values of RR(int), BP(mean), and respiratory frequency did not differ between patients after right- or left-sided stroke and controls (p > 0.05). Patients after right-sided stroke showed a trend toward elevated LF power of RR(int) as compared with patients after left-sided stroke and controls (p < 0.10). HF powers of RR(int) were reduced in patients after right- and left-sided stroke as compared with controls (p < 0.05). LF/HF ratio of RR(int) was elevated in patients after right-sided stroke as compared with patients after left-sided stroke and controls (p < 0.05). CONCLUSION: Irrespective of the side of the ischemia, post-acute stroke patients showed a parasympathetic cardiac deficit. Additionally, sympathetic cardiovascular modulation was increased in patients after right-sided stroke. Post-acute stroke patients might be at an increased risk for cardiac arrhythmia after unopposed sympathetic stimulation.

[Methods of quantitative evaluation of the autonomic nerve system]. / Methoden zur quantitativen Untersuchung des autonomen Nervenystems.

Dysfunction of the autonomic nervous system is a frequent finding in many neurological and internal diseases. The quantitative assessment of cardiovascular and sudomotor function is important for diagnosing the autonomic impairment. In this review article, we focus on standard tests that allow evaluation of cardiovascular and sudomotor autonomic functions and describe methods of quantitative assessment that are better suited for research.

Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy.

BACKGROUND: Peripheral neuropathy in Fabry disease predominantly involves small nerve fibers. Recently, enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A has become available. OBJECTIVE: To evaluate whether ERT improves Fabry neuropathy. METHODS: In 22 Fabry patients (age 27.9 +/- 8.0 years) undergoing ERT with recombinant human alpha-galactosidase A (agalsidase beta) for 18 (n = 11) or 23 (n = 11) months and in 25 control subjects (age 29.0 +/- 10.4 years), the authors performed quantitative sensory testing using the 4, 2, and 1 stepping algorithm (CASE IV). Detection thresholds of vibration (VDT) on the first toe were assessed; cold detection thresholds (CDT), heat-pain onset (HP 0.5), and intermediate heat-pain (HP 5.0) assessments were made on the dorsum of the feet. Patient values above mean + 2.5 SD of control values were considered abnormal. RESULTS: Before ERT, VDT, CDT, HP 0.5, and HP 5.0 were higher in patients than control subjects (p < 0.05). Following ERT, patients developed lower thresholds than prior to ERT for VDT (15.5 +/- 3.5 vs 14.3 +/- 4.1; p < 0.05), HP 0.5 (22.3 +/- 6.7 vs 19.4 +/- 1.3; p < 0.01), and HP 5.0 (27.3 +/- 5.6 vs 22.5 +/- 2.3; p < 0.01). Moreover, fewer patients had abnormal results of VDT (2 vs 4), CDT (7 vs 12), HP 0.5 (0 vs 9), and HP 5.0 (4 vs 20) after than before ERT. CONCLUSIONS: ERT therapy with agalsidase beta significantly improves function of C-, Adelta-, and Abeta-nerve fibers and intradermal vibration receptors in Fabry neuropathy. Lack of recovery in some patients with abnormal cold or heat-pain perception suggests the need for early ERT, prior to irreversible nerve fiber loss.

[Hospitalization of non-stroke patients in a Stroke Unit]. / Einweisung von Nicht-Schlaganfallpatienten auf eine Stroke Unit.

BACKGROUND AND OBJECTIVE: Stroke care in Germany has substantially improved during the last decade. One column of modern stroke care is the institution of stroke unit which allows rapid diagnosis and treatment. The aspect of admission of nonstroke patients to a stroke unit is poorly evaluated. The aim of this study is to evaluate the number of patients who are admitted to a national stroke unit but do not suffer from stroke. Furthermore, we related the proportion of nonstroke referrals to the different referral modes. PATIENT AND METHODS: Observational study recording all suspected stroke referrals with regard to final diagnosis and type of referral during a 12-month period (1.8.2002-31.7.2003). RESULTS: 462 patients were admitted by 4 routes: 74 by paramedics or by self-presentation, 138 by emergency physicians, 144 by primary care doctors, and 106 were transferred from other hospitals. 88 patients (19 %) finally revealed no acute stroke. The most common nonstroke diagnoses were seizure (20 %), dissociative disorders (14 %), cranial nerve disorders (11 %), hypoglycaemia (8 %) and transient global amnesia (7 %). There was no significant difference among the proportion of nonstroke patients referred by ambulance paramedics and self-presentation (15 %), emergency physicians (21 %), primary care doctors (15 %) and interhospital transfer (24 %) [p = 0.222, X (2)-test according to Pearson]. CONCLUSION: Due to the fact that a number of clinical neurological conditions mimic acute stroke, misdiagnosis of stroke is common. We advocate that all stroke patients are seen early in the course of the disease by a neurologist. An alternative could be that in stroke units of internal medicine hospitals patients are seen by a consulting neurologist. Alternatively, telemedicine might be used and the neurologist on duty of a neurological stroke unit could be consulted.

Impaired cardiovagal and vasomotor responses to baroreceptor stimulation in type II diabetes mellitus.

BACKGROUND: In diabetic patients, impairment of the cardiovagal limb of the baroreflex has been well established. However, the role of sympathetic mediated baroreflex vasomotor control of the blood vessels is not well defined. We therefore assessed the vasomotor responses to sinusoidal baroreceptor stimulation in diabetic patients. MATERIALS AND METHODS: We studied 14 type II diabetic patients (age; 57 +/- 7 years) and 18 healthy controls (age; 59 +/- 11 years). Oscillatory neck suction was applied at 0.1 Hz to assess the sympathetic modulation of the heart and blood vessels, and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Breathing was paced at 0.25 Hz. Spectral analysis was used to evaluate the oscillatory responses of RR-interval and blood pressure. RESULTS: The diabetic patients showed a significantly lower RR-interval response (P < 0.05) to the 0.1 Hz neck suction (2.52 +/- 0.50-3.62 +/- 0.54 ln ms2) than the controls (4.23 +/- 0.31-6.74 +/- 0.36 ln ms2). The increase in power of 0.1 Hz systolic blood pressure oscillations during 0.1 Hz suction was also significantly smaller (P < 0.05) in the diabetics (1.17 +/- 0.44-1.69 +/- 0.44 mmHg2) than in the controls (1.60 +/- 0.29 mmHg2-5.87 +/- 1.25 mmHg2). The magnitude of the peak of the 0.2 Hz oscillation in the RR-interval in response to 0.2 Hz neck stimulation was significantly greater (P < 0.05) in the controls (3.42 +/- 0.46 ln ms2) than in the diabetics (1.58 +/- 0.44 ln ms2). CONCLUSION: In addition to cardiovagal dysfunction, baroreflex-mediated sympathetic modulation of the blood vessels is impaired in type II diabetic patients.

Small fiber dysfunction predominates in Fabry neuropathy.

Fabry disease is an X-linked recessive disease with a reduction of lysosomal alpha galactosidase A and consecutive storage of glycolipids e.g., in the brain, kidney, skin, and nerve fibers. Cardinal neurologic findings are hypohidrosis, painful episodes, and peripheral neuropathy. So far, the neurophysiological findings regarding the extent of large and small fiber dysfunction are contradictory. This study evaluated large and small nerve fiber function in a homogeneous group of Fabry patients. In 24 of 30 Fabry patients with creatinine below 194.7 mmol/L the authors assessed median, ulnar, and peroneal motor conduction velocity (MCV) and median, ulnar, and sural sensory conduction velocity (SCV) nerve conduction to study the function of thickly myelinated nerve fibers. In addition, the authors studied sympathetic skin responses (SSR) at both hands and feet in 24 patients. To evaluate A beta nerve fiber function, the authors determined vibratory detection thresholds (VDT) at the first toe in 30 patients. Function of A delta and C fibers was assessed by quantitative sensory testing of cold detection threshold (CDT) and heat-pain detection thresholds (HPDT). Nerve conduction studies showed significantly decreased amplitudes of MCVs and SCVs in Fabry patients as compared to controls. However, individual results of MCV and SCV studies were only mildly impaired. SSRs were present in all tested patients but SSR amplitudes were significantly decreased in Fabry patients in comparison to controls. VDT, CDT, and HPDT were significantly elevated in Fabry patients as compared to controls. However, only six patients had pathologic VDT, 19 had increased CDT, and 25 had elevated HPDT at a high level of stimulation. In Fabry patients, small fiber dysfunction is more prominent than large fiber dysfunction, confirming previous findings of sural nerve biopsies. The results suggest a higher vulnerability of small-diameter nerve fibers than of the thickly myelinated fibers.

Decrease of sympathetic cardiovascular modulation after temporal lobe epilepsy surgery.

In temporal lobe epilepsy (TLE), there is evidence of ictal and interictal autonomic dysregulation, predominantly with sympathetic overactivity. The effects of TLE surgery on autonomic cardiovascular control and on baroreflex sensitivity (BRS) have not been studied. To evaluate such effects, we monitored heart rate (HR), systolic blood pressure (BP(sys)) and respiration in 18 TLE patients 3-4 months before and after TLE surgery. We used Blackman-Tukey spectral analysis to assess sympathetic and parasympathetic modulation as powers of HR and BP(sys) oscillations in the low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) bands. BRS was determined as the LF transfer function gain between BP and HR. After surgery, HR, BP(sys), respiration and HF powers remained unchanged, while LF powers of HR (1.57 +/- 1.54 bpm(2)) and BP(sys) (2.19 +/- 1.34 mmHg(2)) and BRS (0.68 +/- 0.31 bpm/mmHg) were smaller than pre-surgical LF powers of HR (3.87 +/- 3.26 bpm(2)) and BP(sys) (4.80 +/- 3.84 mmHg(2)) and BRS (1.12 +/- 0.39 bpm/mmHg; P < 0.05). After TLE surgery, there is a reduction of sympathetic cardiovascular modulation and BRS that might result from decreased influences of interictal epileptogenic discharges on brain areas involved in cardiovascular autonomic control. TLE surgery seems to stabilize the cardiovascular control in epilepsy patients by reducing the risk of sympathetically mediated tachyarrhythmias and excessive bradycardiac counter-regulation, both of which might be relevant for the pathophysiology of sudden unexpected death in epilepsy patients (SUDEP). Thus, TLE surgery might contribute to reducing the risk of SUDEP.

Sympathetic and parasympathetic pupillary dysfunction in familial dysautonomia.

Objective assessment of autonomic dysfunction in familial dysautonomia (FD) is largely based on the analysis of cardiovascular responses to challenge maneuvers such as orthostatic stress. Infrared pupillometry (IPM) provides an additional reliable method for cranial autonomic evaluation and has the advantage of requiring minimal cooperation.This study was performed to determine whether IPM contributes to the assessment of autonomic function in FD patients. In 14 FD patients and 14 healthy controls, we studied absolute and relative light reflex amplitude, pupillary constriction velocity (v(constr)), pupillary diameter, early and late pupillary re-dilatation velocity (v(dil 1), v(dil 2)) after dark adaptation. Prior to IPM, all patients had an ophthamological examination to evaluate refraction and corneal integrity. In comparison to controls, patients had a significant reduction of the parameters reflecting parasympathetic pupillary function (absolute light reflex amplitude 1.34 +/- 0.21 vs. l.86 +/- 0.14 mm, relative light reflex amplitude 22.74 +/- 7.11% vs. 30.76 +/- 3.57%, v(constr) 3.75 +/- 1.09 vs. 5.80 +/- 0.59 mm/s) and of the parameters reflecting sympathetic pupillary function (diameter 5.69 +/- 0.66 vs. 6.35 +/- 0.60 mm, v(dil 1) 1.29 +/- 0.23 vs. 1.95 +/- 0.23 mm/s, v(dil 2) 0.64 +/- 0.13 vs. 0.72 +/- 0.l2 mm/s; Mann-Whitney U-test: p<0.05). The non-invasive technique of IPM demonstrates dysfunction not only of the cranial parasympathetic, but also of the cranial sympathetic nervous system and, thus, further characterizes autonomic dysfunction in FD.