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.

[The new S2k AWMF guideline for the treatment of Bell's palsy in commented short form]. / Die neue S2k AWMF Leitlinie zur idiopathischen Fazialisparese in kommentierter Kurzform.

A new S2k AWMF guideline for the treatment of idiopathic facial palsy has been published. An accurate differential diagnosis is indispensable as 25-40% of all facial palsy cases are of non-idiopathic origin. It is explicitly recommended to treat patients with idiopathic facial palsy with steroids. Steroids favour a complete recovery, decrease the risk of synkinesis, autonomic sequelae and contractures. Adjuvant antiviral therapy cannot be recommended. On current data there is not sufficient evidence that the combination of steroids with antiviral drugs has a benefit for the patients. Even when not supported by randomized trials, adjuvant symptomatic therapy to protect the cornea and to avoid complications is recommended. There is no scientific evidence that physical therapy has any benefit but it should be taken into account because of psychological reasons. A benefit of acupuncture has not been proven. If eye closure remains incomplete as result of defective healing, one therapeutic option is lid loading of the upper eye lid. Moreover, in case of severe persistent palsy, several well-established microsurgical nerve and muscle plasty procedures are available.

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.

[OSCE in the neurology clerkship. Experiences at the neurological department of the university hospital Erlangen]. / OSCE in der Neurologie. Erfahrungen an der neurologischen Universitätsklinik Erlangen.

BACKGROUND: In the German medical education program practical examinations at the end of the neurology clerkship are sparsely performed. By this way, motivation for practical learning and a method to assure quality of learning are not used. METHOD: The Anglo-Saxon concept of "objective structured clinical examination" (OSCE) is picked up and implemented as a practical examination at the end of the neurology clerkship of medical students in their 4th and 5th year. A catalogue of learning goals was defined and an OSCE of 5 stations was developed. A standard of a successful examination was defined. In two OSCE stations the competence in clinical decision making and reasoning were tested, in two stations the competence in practical examination skills and in one station the practical skill to perform a lumbar puncture at the phantom. The results of the OSCE stations were analysed for task difficulty, discriminatory power, normalized discrimination index and reliability. Using a questionnaire, the students evaluated the OSCE. RESULTS: N = 123 students (73 female, 50 male) with a mean age of 26.1 years (22 - 46 years) participated. The mean score was 40 +/- 3.6 of a total of 50 points (range 29 - 46). Female students (40.8 +/- 3.1) scored significantly higher than male ones (38.8 +/- 4; p = .002). One student (0.8 %) failed the examination. The difficulty of the stations ranged between 0.63 and 0.91, normalized discrimination index between 0.1 and 0.18 and the discriminatory power from r = 0.25 to r = 0.53. The reliability of the 5 stations was 0.65 (Cronbach's alpha). In the evaluation, the rating for innovation, organisation, length, clarity of the tasks, clinical reality and compatibility with general physician's competence, atmosphere during the examination and fairness was extremely positive. Most students would prefer an OSCE compared with a multiple-choice test. CONCLUSION: An OSCE at the end of the neurology clerkship is feasible. The quantitative analyses of the results are concordant with requirements of medical examinations. The OSCE is positively evaluated by the students.

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.

Taste in dementing diseases and parkinsonism.

Like with many sensory abilities a reduction of taste and smell occurs during aging. Since there are hints to an additional reduction in dementing diseases, we assessed 52 patients, 26 women and 26 men, who were presented to a memory clinic, using the Sniffin' Sticks, Whole Mouth and Taste Strip Tests. While smoking, alcohol consumption, intake of drugs and sex exerted only minor impact, age and the severity of cognitive impairment were of major importance. There was a moderate but significant correlation between the severity of dementia, taste and smell, even if the age effect was partialled out. Notably, patients with Parkinson syndrome showed worse taste and smell abilities than those without. Here the differences were indeed marked enough to play a possible role in making the diagnosis. This exploratory study confirms a mild reduction of gustatory function in dementing diseases over and beyond that of normal aging which--in addition to a reduction of smell--seems to be especially marked in Parkinson syndromes.

Zinc gluconate in the treatment of dysgeusia--a randomized clinical trial.

In the treatment of dysgeusia, the use of zinc has been frequently tried, with equivocal results. The aim of the present randomized clinical trial, which involved a sufficiently large sample, was therefore to determine the efficacy of zinc treatment. Fifty patients with idiopathic dysgeusia were carefully selected. Zinc gluconate (140 mg/day; n=26) or placebo (lactose; n=24) was randomly assigned to the patients. The patients on zinc improved in terms of gustatory function (p <0.001) and rated the dysgeusia as being less severe (p <0.05). Similarly, signs of depression in the zinc group were less severe (Beck Depression Inventory, p <0.05; mood scale, p <0.05). With the exception of the salivary calcium level, which was higher in the zinc patients (p <0.05), no other significant group differences were found. In conclusion, zinc appears to improve general gustatory function and, consequently, general mood scores in dysgeusia patients.

Recognition of familiar handwriting in stroke and dementia.

Patients with left stroke (n = 17), right stroke (n = 16), and dementia (n = 17) and healthy controls (n = 15) were asked to recognize familiar handwriting among 10 handwritten texts. All healthy controls and 96% of the left-brain-damaged patients were able to recognize the familiar handwriting, but only 44% of the right-brain-damaged and 41% of the dementia patients (none if Mini-Mental Status Test score was <18, n = 5) were able to do so. The authors conclude that the recognition of handwriting is a special skill that is independent of other verbal and lexical tasks.

Oral mucosal blood flow in patients with burning mouth syndrome.

The pathophysiology of burning mouth syndrome (BMS) is largely unknown. Thus, the aim was to study oral mucosal blood flow in BMS-patients using laser Doppler flowmetry (LDF). Thirteen BMS patients (11 female, two male; mean age+/-SD 64.3+/-7.9 years, mean disease duration 18.9+/-6.2 months) and 13 healthy non-smoking controls matched for age and gender (11 female, two male; mean age 64.7+/-8.1 years) were investigated. Using the LDF technique mucosal blood flow (mBF) was measured at the hard palate, the tip of the tongue, on the midline of the oral vestibule, and on the lip. Measurements were made at rest and over 2 min following dry ice application of 10 s duration using a pencil shaped apparatus. In addition, blood pressure (BP), heart rate (HR), peripheral cutaneous blood flow, and transcutaneous pCO(2) were continuously recorded. Mucosal blood flow (mBF) increased at all measurement sites in response to dry ice application (P<0.001) with peak flow at 0.5--1.5 min after stimulation onset. During the following 1.5--2 min, blood flow decreased at all sites with a tendency to return to baseline towards the end of the observation period. Except for BP and peripheral blood flow, all of the cardiovascular changes exhibited significant changes during the observation period; no differences between groups were detected. When compared to healthy controls BMS patients generally exhibited larger changes in mBF. These changes were significant for recordings made on the hard palate (F[1,24]=13.9, P<0.001). Dry ice stimulation appears to be an effective, non-invasive and reasonably tolerable means to investigate mucosal blood flow at different mucosal sites. In general, vasoreactivity in BMS patients was higher than in healthy controls. BMS patients exhibited a higher response on the hard palate compared to controls. These changes in oral blood flow appear to be specifically related to BMS symptoms indicating a disturbed vasoreactivity.

Neurological manifestations of chronic hepatitis C.

Hepatitis C virus (HCV) infection is often associated with abnormal immunological responses. We describe four patients with vasculitic neurological signs and symptoms following HCV infection. A 56-year-old woman with HCV infection developed peripheral neuropathy characterized by asymmetric distal painful hypesthesia, dysesthesia and moderate motor weakness of the lower limbs. Serological examinations revealed cryoglobulinemia and low levels of complement C4. A biopsy of the sural nerve revealed vasculitic neuropathy. HCV infection associated immunomediated vasculitis was diagnosed. While steroid therapy was ineffective, treatment with interferon-alpha improved the neuropathy considerably without, however, eliminating HCV infection. A 62-year-old man with HCV infection developed peripheral sensory neuropathy. Complement C3 was slightly diminished. Nerve biopsy revealed vasculitic neuropathy. A 71-year-old woman developed chronic symmetric sensomotor polyneuropathy. HCV hepatitis followed blood transfusions. Cryoglobulins tested positive, consistent with type II cryoglobulinemia. Complements C3 and C4 were diminished. Inflammatory infiltrates in the sural nerve biopsy specimen led to the diagnosis of chronic vasculitic disorder. A 55-year-old woman with HCV infection developed vasculitis of the skin, connective tissue, visceral organs, and kidney, leading to hemodialysis. Neurologically she developed severe apathy and drowsiness, myoclonic jerks, exaggerated deep tendon reflexes, and positive pyramidal signs. Magnetic resonance imaging of the brain showed diffuse increased signal abnormalities involving supra- and infratentorial white matter suggesting cerebral vasculitis. Cryoglobulins were positive, complements C3 and C4 slightly diminished (54 mg/dl, 4.3 mg/dl). Supportive therapy resulted in neurological improvement. Treatment with interferon-alpha was discontinued because of agranulocytosis. In patients with peripheral neuropathy or signs of leucencephalopathy, a hepatitis C associated vasculitis should be considered in the differential diagnosis.

Creutzfeldt-Jakob disease via dural and corneal transplants.

A review of all published cases of iatrogenic Creutzfeldt-Jakob disease (CJD) via dural (N=71) and corneal (N=4) transplants is given. All but three of the dural cases were obviously due to a commercial product recalled in 1996. Two of the corneal grafts were taken from patients who had died of sporadic CJD. These cases differed from CJD due to human growth hormone injections and the new variant. Instead. they were akin to sporadic cases, but memory loss, disorders of higher cerebral functions and extrapyramidal signs were fewer, while cerebellar abnormalities were more frequent. Progressive dysarthria and gait disorder/gait ataxia were prominent signs during the early stages, myocloni the most salient feature later. A nonperiodic EEG did not contradict the diagnosis. Using current diagnostic criteria the disease was underdiagnosed ante mortem. Utmost care is needed in selecting, harvesting and handling dural and corneal grafts to avoid inadvertent transmission of CJD.

Transcranial doppler sonography-ergometer test for the non-invasive assessment of cerebrovascular autoregulation in humans.

Cerebrovascular hemodynamics during physical stress have been sparsely investigated, mostly through risky invasive techniques. The aim of this study was to determine the effect of ergometer stress on cerebrovascular hemodynamics in humans using the non-invasive and thus clinically-applicable method of transcranial Doppler sonography (TCD) combined with simultaneous non-invasive measurements of cardiovascular parameters. In eighteen healthy subjects (six women, twelve men; 29.3+/-4.6 years old) left midcerebral artery blood flow velocities (CBFVs) were continuously monitored using TCD during 3 min at rest, 3 min during ergometry and 3 min recovery. Simultaneously, systolic, diastolic, mean CBFVs, pulsatility index (PI), heart rate, beat-to-beat blood pressure (BP) and transcutaneous p(CO(2)) were measured. The subjects were supine with elevated trunk. Ergometry was performed by pedalling a Mühe-ergometer. In eight volunteers, the procedure was repeated within the next day to test the repeatability of the results. Heart rate increased significantly during ergometry (from 65.2+/-11 to 105. 3+/-12.3/min; P<0.05). The systolic BP increased significantly slightly later during ergometry (from 118.9+/-8.6 to 141.6+17.9 mmHg; P<0.05). Transcutaneous p(CO(2)) was initially within physiological ranges, but increased significantly after a delay during the 3rd min of cycling (from 39.7+/-3.7 to 41.1+/-4.7 mmHg; P<0.05). MFV started to rise significantly after 1 min of the exercise period (from 59.6+10.9 to 68.3+13.9 cm/s; P<0.05). PI increased immediately and significantly at the start of exercise (PI at rest 0.93+0.11; PI ergometry 1.1+0.13; P<0.05). The results were found to be reproducible in the eight volunteers. The cerebrovascular changes during ergometer exercise may reflect the combined activation of the cerebrovascular autoregulative mechanisms (neurogenic, myogenic and metabolic). The TCD-ergometer test presented here is non-invasive and would seem to present a low risk for patients who are judged fit enough for mild exercise. The test may contribute to the detection of cerebrovascular abnormalities in various diseases.

Transcranial Doppler sonography during acute 80 degrees head-down tilt (HDT) for the assessment of cerebral autoregulation in humans.

Cerebrovascular hemodynamics during postural changes have been sparsely investigated despite the fact that abnormal responses may contribute to the risk of stroke. The aim of this study was to determine the effect of acute 80 degrees head-down tilt (HDT) on cerebrovascular hemodynamics in humans using transcranial Doppler sonography (TCD). In 13 healthy volunteers (2 female, 11 male, age 19-37 years, mean age 26.8 years) left midcerebral artery blood flow velocities (CBFVs) were continuously monitored using TCD during 180 sec in horizontal position and during 60 sec of 80 degrees HDT. Simultaneously, systolic, diastolic, mean CBFVs, pulsatility index (PI), heart rate, beat-to-beat blood pressure (BP) and transcutaneous pCO2 were measured. In five volunteers, the procedure was repeated the next day to test the repeatability of the results. Mean BP increased slightly, but not significantly during tilt (from 80.5 +/- 7.7 mmHg to 85.9 +/- 14.1 mmHg; p > 0.05). Heart rate decreased significantly during the first 20 sec of HDT (from 66.8 +/- 9.9 min-1 to 60 +/- 11 min-1; p < 0.05). Transcutaneous pCO2 was within physiological ranges during the whole procedure (mean pCO2 minimum 39.5 +/- 2.9 mmHg, mean pCO2 maximum 42.2 +/- 3.3 mmHg). Mean CBFV did not change significantly during tilt (from 70.1 +/- 19.1 cm sec-1 to 66.6 +/- 14.1 cm sec-1; p > 0.05). PI, however, increased significantly with a more pronounced increase during the first 20 sec than the last 40 sec of tilt (PIsupine 0.92 +/- 0.11; PItilt(0-20 sec) 1.15 +/- 0.18; PItilt(21-60 sec) 1.03 +/- 0.16; p = 0.001; p = 0.017). The HDT results were found to be reproducible in the five volunteers. During 80 degrees-HDT mean BP and pCO2 did not change significantly. This observation combined with the significant decrease in heart rate during the first 20 sec of HDT, suggests that there is no sympathetic activation. The significant PI increase during HDT indicates a vasoconstriction of the cerebral resistance vessels. We assume that this vasoconstriction is due to the myogenic mechanism of cerebrovascular autoregulation triggered by a rapid, passive intracranial blood volume influx during HDT.

Transcranial Doppler sonography during acute 80° head-down tilt (HOT) for the assessment of cerebral autoregulation in humans.

Cerebrovascular hemodynamics during postural changes have been sparsely Investigated despite the fact that abnormal responses may contribute to the risk of stroke. The aim of this study was to determine the effect of acute 80° head-down tilt (HDT) on cerebrovascular hemodynamics in humans using transcranial Doppler sonography (TCD). In 13 healthy volunteers (2 female, 7 1 male, age 19-37 years, mean age 26.8 years) left midcerebral artery blood flow velocities (CBFVs) were continuously monitored using TCD during 180 sec in horizontal position and during 60 sec of 80° HDT. Simultaneously, systolic, diastolic, mean CBFVs, pulsatility index (PI), heart rate, beat-to-beat blood pressure (BP) and transcutaneous pC02 were measured. In five volunteers, the procedure was repeated the next day to test the repeatability of the results. Mean BP increased slightly, but not significantly during tilt (from 80.5± 7.7 mmHg to 85.9 ±14.1 mmHg; p < 0.05). Heart rate decreased significantly during the first 20sec of HDT (from 66.8± 9.9 min-1 to 60± 11 min-1; p> 0.05). Transcutaneous pC02 was within physiological ranges during the whole procedure (mean pC02 minimum 39.5±2.9 mmHg, mean pC02 maximum 42.2±3.3 mmHg). Mean CBFV did not change significantly during tilt (from 70.1 ± 7 9.1 cm sec-1 to 66.6 ± 14.1 cm sec-1; p < 0.05). PI, however, increased significantly with a more pronounced increase during the first 20 sec than the last 40sec of tilt (Plsupine 0.92±0.11; Pltnt(0-20sec) 1.15±0.18; Pltnt(2i~6o sec) 1-03±0.16; p = 0.001; p = 0.017). The HDT results were found to be reproducible in the five volunteers. During 80°-HDT mean BP and pC02 did not change significantly. This observation combined with the significant decrease in heart rate during the first 20 sec of HDT, suggests that there is no sympathetic activation. The significant PI increase during HDT indicates a vasoconstriction of the cerebral resistance vessels. We assume that this vasoconstriction is due to the myogenic mechanism of cerebrovascular autoregulation triggered by a rapid, passive intracranial blood volume influx during HDT. [Neurol Res 1999; 21: 457-462].

Ondine's curse in association with diabetes insipidus following transient vertebrobasilar ischemia.

Ischemic lesions of the brainstem can lead to complex neurologic deficits. Failure of the automatic control of ventilation (Ondine's curse syndrome) is a possible but rare syndrome following localized brainstem dysfunction. We report on a 49-year-old man with intermittent bradycardia, cranial nerves' dysfunctions and a slight right-sided hemiparesis. An acute brainstem ischemia was diagnosed and treated immediately with high-dose heparin. Cerebral angiography revealed a proximal occlusion of the left vertebral artery but a normal right vertebral artery and a hyperplastic right posterior inferior cerebellar artery. Cranial Computed Tomography and MRI scan demonstrated multiple ischemic lesions in the posterior circulation. During a 4-week treatment course the patient underwent six episodes of acute severe hypoxia and hypercapnia requiring orotracheal intubation twice and manual ventilation by air mask over a few minutes for four times after a tracheostomy had been performed. Twice a short-term episode of hypothalamic Diabetes insipidus was observed following hypoventilation. We conclude that both Ondine's curse syndrome and diabetes insipidus were due to transient vertebrobasilar ischemia.

Cerebral vein thrombosis and prothrombin gene (G20210A) mutation.

Recently, prothrombin gene mutation G20210A has been associated with elevated thrombosis risk and rarely with cerebral vein thrombosis (CVT). Three patients are described who had this genetic predisposition and who developed CVT in an unusual constellation with other factors. In the first patient, the intake of valproic acid (VPA) may have played an aggravating role in the development of CVT; in the second patient diagnosis of coagulation disorder was made during pregnancy consultation 6 years after CVT; in the third patient the CVT occurred at the age of 78 years. In patients with CVT, coagulation-examinations should include tests for the prothrombin gene (G20210A) mutation.

Progression of optic neuritis to multiple sclerosis: an 8-year follow-up study.

OBJECTIVE: The relationship between acute monosymptomatic optic neuritis (AON) and subsequent multiple sclerosis (MS) is still doubtful. We investigated the risk of developing MS in patients from North Bavaria, who were suffering from AON. PATIENTS/METHODS: Twenty-nine patients with clinical evidence of AON were included in the study. Initial evaluation included brain resonance imaging (MRI) and a clinical neurological examination. Follow-up examinations were performed after 72-108 months (mean: 96 months) in 26 patients (three patients were lost to follow-up) and consisted of a second complete neurological examination. Diagnosis of MS was established according to the criteria of Poser CM, Paty DW, Scheinberg L. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983:13:227-231. RESULTS: At follow-up, 14 of 26 patients (54%) had converted to clinically definite MS. Nine patients (64%) had developed MS within 2 years after the onset of AON. CONCLUSION: We observed the development of MS in 54% of the 26 investigated AON patients. The exceptional feature of the present study was the relatively long follow-up period of 8 years.

Severe neurological complications of ulcerative colitis.

A 37 year old man presented with a 15 year history of ulcerative colitis. On examination he had weakness of the right arm, slurred speech and progressive confusion, followed by a rapid deterioration of consciousness and motor functions resulting in coma, tetraparesis and bilateral Babinski responses. Magnetic resonance imaging of the brain and spinal cord revealed multiple hyper- and hypointense white matter lesions. Clinical symptoms, history and neuroradiological findings led to the diagnosis of an ulcerative colitis-associated CNS disorder. An autoimmune vasculitic process may have played an important pathophysiological role, considering the vasculitic changes observed by skin biopsy as well as the rapid clinical improvement following immunosuppressive therapy with corticosteroids and azathioprine. During a follow up period of more than one year we observed continuous and complete recovery of neurologic symptoms.