EFNS/ENS Guidelines for the treatment of ocular myasthenia.

BACKGROUND AND PURPOSE: The symptoms of acquired autoimmune ocular myasthenia are restricted to the extrinsic eye muscles, causing double vision and drooping eyelids. These guidelines are designed to provide advice about best clinical practice based on the current state of clinical and scientific knowledge and the consensus of an expert panel. SEARCH STRATEGY: Evidence for these guidelines was collected by searches in the MEDLINE and Cochrane databases. The task force working group reviewed evidence from original articles and systematic reviews. The evidence was classified (I, II, III, IV) and consensus recommendation graded (A, B or C) according to the EFNS guidance. Where there was a lack of evidence but clear consensus, good practice points are provided. CONCLUSIONS: The treatment of ocular myasthenia should initially be started with pyridostigmine (good practice point). If this is not successful in relieving symptoms, oral corticosteroids should be used on an alternate-day regimen (recommendation level C). If steroid treatment does not result in good control of the symptoms or if it is necessary to use high steroid doses, steroid-sparing treatment with azathioprine should be started (recommendation level C). If ocular myasthenia gravis is associated with thymoma, thymectomy is indicated. Otherwise, the role of thymectomy in ocular myasthenia is controversial. Steroids and thymectomy may modify the course of ocular myasthenia and prevent myasthenia gravis generalization (good practice point).

Good long-term efficacy of pallidal stimulation in cervical dystonia: a prospective, observer-blinded study.

BACKGROUND AND PURPOSE: Deep brain stimulation of the internal globus pallidus (GPi-DBS) is established as an effective treatment of primary generalised dystonia in controlled studies. In cervical dystonia (CD), only one previous study has reported observer-blinded outcome assessment of long-term GPi-DBS, with 1-year follow-up. METHODS: In this prospective, single-centre study, eight patients with CD (7 women:1 man, 4 focal:4 segmental) treated with bilateral GPi-DBS for median (range) 30 (12-48) months, were evaluated by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS; Severity, Disability and Pain scores), the Short-Form Health Survey-36 (SF-36), and the Becks Depression Index in an open design. In addition, a blinded rater assessed the TWSTRS Severity score from videos obtained preoperatively and at the last follow-up. RESULTS: In the blinded evaluation, median (range) TWSTRS Severity score improved from 25 (19-30) to 8 (4-23) (P = 0.028), thus a 70% (23-82) score reduction. In the open evaluation, median Severity score improvement at the last follow-up was 73%, representing a significant further improvement from 50% at 6 months. The Disability and Pain scores improved by median 91% and 92%, respectively, and the SF-36 subdomain scores improved significantly. A reversible right hemiparesis and aphasia occured in one patient 4 days postoperatively, because of reversible oedema around the left electrode. No other serious adverse effects and no permanent morbidity were observed. CONCLUSIONS: This single-blinded study shows good long-term efficacy of GPi-DBS in CD patients and supports using this treatment in those who have insufficient response to medical treatment.

Does cardiovascular autonomic dysfunction contribute to fatigue in myasthenia gravis?

Myasthenia gravis (MG) is an autoimmune disease characterized by fatigable muscle weakness. Despite full spontaneous or pharmacological remission some MG patients still complain of physical and mental fatigue. Fatigue has been related to autonomic dysregulation. The aim of this study was to assess autonomic responses in a group of MG patients in complete remission but complaining of persistent fatigue. Seventeen well-regulated but persistently fatigued MG patients and 17 individually matched controls underwent echocardiography assessing systolic and diastolic heart function. Beat to beat cardiovascular responses at rest and to 30o head-up tilt, tilt-back, and 2-min static handgrip contraction were recorded. Fatigued MG patients had a statistically significant higher resting HR than their matched controls (p=0.03). The difference in resting heart rate between MG patients not using acetylcholine esterase inhibitors (AChEi) and their matched controls was even more pronounced (p=0.007). The autonomic cardiovascular adjustments to head-up tilt, tilt-back and handgrip contraction were not statistically significant different between patients and controls. We found a higher resting heart rate in all well-regulated but fatigued MG patients compared with controls. The difference was more pronounced between patients not taking AChEi compared to their matched controls. This finding may reflect a disturbed resting sympathovagal balance and this might be a contributing factor to the fatigue symptoms.

Periodic abducens nerve palsy in adults caused by neurovascular compression.

Unilateral abducens nerve palsy with periodic recurrences is a well-recognised finding in children, but is rare in adults. The underlying pathophysiological mechanism is unknown. Vascular compression of the nerve is suspected but never demonstrated. We describe an adult patient with, altogether, 11 periods of unilateral right-sided abducens palsy and arterial contact at the root exit zone of the symptomatic side.

Determinants and status of quality of life after long-term botulinum toxin therapy for cervical dystonia.

The aim of this study was to assess health-related quality of life (HRQoL), using the Short Form Health Survey-36 (SF-36), in 70 cervical dystonia (CD) patients after long-term botulinum toxin (BTX) treatment (median 5.5 years), and to identify factors determining reduced HRQoL. We used combined patient-and physician-based measures to assess both CD severity [Toronto Western Spasmodic Torticollis Rating Scale, (TWSTRS)] and effect of long-term BTX treatment, and the Hospital Anxiety and Depression Scale (HAD) and General Health Questionnaire-30 to assess psychological distress. Mean SF-36 domain scores of the CD patients were reduced by <1 SD compared with age- and gender-matched population samples. High TWSTRS total scores and high HAD-depression (HAD-D) scores were the main factors associated with reduced scores in the physical and mental SF-36 domains, respectively. Patients evaluated to have a 'good effect' of long-term BTX treatment (n = 47), had significantly lower median TWSTRS total score, and a 3x lower frequency of high HAD-D scores, than those evaluated to an 'unsatisfactory effect' (n = 23). In conclusion, most CD patients enjoy a good HRQoL after long-term BTX therapy. Reduced HRQoL was associated with more severe disease and/or depressive symptoms.

Microvascular decompression for hemifacial spasm: postoperative neurologic follow-up and evaluation of life quality.

Microvascular decompression (MVD) is an effective and safe treatment in hemifacial spasm (HFS). Postoperative evaluations are usually made by neurosurgeons. Follow-up studies performed by neurologists and postoperative quality of life (QoL) investigations are lacking. All 25 HFS patients operated with MVD in our centre between 2000 and 2004 were evaluated with the recently validated HFS-7 scheme, extended with the item 'sleep disturbance due to HFS' (HFS-8). The patients underwent a careful neurological examination median 3 years after the operation. The evaluation focused on clinical aspects, changes in blood pressure and time until observable effect of MVD. The evaluation of HFS-7 questionnaire and the extended form (HFS-8) showed significant improvement in QoL after MVD. Neurological outcome was in almost all cases excellent or good. Eleven (44%) patients had no neurological deficits at all. Only one patient had serious complications with ipsilateral facial palsy, deafness, balance problems and vertigo. The other patients had minor neurological findings or symptoms. Eighteen (72%) patients experienced early effect within 3 months after MVD; seven (28%) patients had late effect between 6 and 14 months. Median age of the patients with late effect (62.6 years) was significantly higher than in those with early effect (52.7 years).

Juvenile myasthenia gravis in Norway: Clinical characteristics, treatment, and long-term outcome in a nationwide population-based cohort.

BACKGROUND: This study aimed to characterize juvenile myasthenia gravis in a national population-based cohort in Norway, and to evaluate long-term outcome and potential differences correlated with prepubertal versus postpubertal disease onset. PATIENTS AND METHODS: Patients with onset of myasthenia gravis aged ≤18 years were identified through multiple strategies. Retrospective clinical data were collected by means of medical charts. All patients had an updated clinical examination. Cases were divided into prepubertal and postpubertal onset using age 12 years as the cut off. RESULTS: In total, 75 patients were identified of whom 63 were included in the study: 21 in the prepubertal and 42 in the postpubertal onset group. There was a female preponderance in both groups. In total, 59% presented with ocular symptoms, but the great majority of patients in both groups generalized during the two first years of the disease. Myasthenic crisis was more frequent in the prepubertal onset group. All patients were initially treated with pyridostigmine, 26 with steroids, and 17 with other immunosuppressive treatment. The postpubertal cases were more often treated with immunosuppressive therapy. Fifty patients (79%) underwent thymectomy. The general outcome was favourable: 57% became asymptomatic and only four subjects failed to attain clinical improvement. One-third had at least one additional autoimmune disease. CONCLUSION: Despite frequent symptom generalization and a subgroup of prepubertal onset with severe disease, the long-term outcome was good, especially in the thymectomized prepubertal onset group. Polyautoimmunity occurred in both groups in one-third.

Juvenile myasthenia gravis in Norway: HLA-DRB1*04:04 is positively associated with prepubertal onset.

BACKGROUND: Juvenile myasthenia gravis (MG) is a rare autoantibody mediated autoimmune disorder targeting the neuromuscular endplate. The clinical hallmark is muscle weakness and fatigability. Disease aetiology is complex, including both genetic and environmental factors. The involvement of genes in the human leukocyte antigen (HLA) is well established in adult MG. However, HLA associations in European juvenile MG have not been studied. This case-control study aimed to investigate and characterize genetic risk factors in prepubertal and postpubertal onset juvenile MG. METHODOLOGY/PRINCIPAL FINDINGS: A population based Norwegian cohort of 43 juvenile MG patients (17 with prepubertal onset, 26 with postpubertal onset) and 368 controls were included. Next generation sequencing of five HLA loci (HLA-A, -B, -C, -DRB1 and -DQB1) was performed, and a positive association was seen with HLA-B*08 (OR (95% CI) = 3.27 (2.00-5.36), Pc = 0.00003) and HLA-DRB1*04:04 (OR (95% CI) = 2.65 (1.57-4.24), Pc = 0.03). Stratified in postpubertal and prepubertal onset, HLA-DRB1*04:04 was only positively associated with the latter (P = 0.01). The HLA-B*08 allele (12.9% in the controls), previously described associated with early onset adult MG, was most frequently observed in postpubertal onset MG (40.4%, P = 0.0002) but also increased among prepubertal onset MG (23.5%, P = 0.05). CONCLUSION: This study provides novel information about HLA susceptibility alleles in Norwegian juvenile MG where HLA-DRB1*04:04 was associated with prepubertal onset.

Juvenile myasthenia gravis in Norway: A nationwide epidemiological study.

BACKGROUND: The aim of this study was to assess the incidence rate and prevalence of autoimmune myasthenia gravis (MG) among children in Norway. METHODS: This retrospective population-based study was performed in Norway from January 2012 to December 2013. Cases of juvenile MG (JMG) with onset < 18 years were identified through searches in coding systems of electronic patient records at the 15 main hospitals in Norway from 1989 to 2013. In addition, the acetylcholine receptor antibody database at Haukeland University Hospital and the clinical nationwide MG database at Oslo University Hospital were searched for cases of JMG. Diagnosis and age at onset were verified through medical records. Incidence and prevalence rates were calculated using the Norwegian population as reference. RESULTS: In total 63 unique JMG cases were identified. This corresponds to an average annual incidence rate of 1.6 per million. Incidence rate was stable over the study period. Prevalence of JMG was 3.6-13.8 per million. Females constituted the majority of JMG cases (55 vs 8 males). The risk of JMG was higher among females both in the postpubertal and prepubertal group (p < 0.001 and p = 0.02, respectively). CONCLUSION: This study confirms the rarity of JMG in Norway, especially among males, and shows a stable incidence rate over the last 25 years.

Apraxia of eyelid opening: clinical features and therapy.

PURPOSE: Botulinum toxin injection is the treatment of choice in cases of benign essential blepharospasm. However, about 10% of the patients do not get sufficient effect from this treatment, and many of them have concomitant apraxia of lid opening. METHODS: Over a 3-year period we treated 12 patients. Three had pure apraxia of lid opening and in the other nine it was associated with blepharospasm. All patients were initially treated with botulinum toxin injections with poor results. They underwent surgical treatment like blepharoplasty, limited myectomy, aponeurosis repair, and/or frontalis suspension. Some of them needed post operative botulinum toxin injections in the pretarsal part of orbicularis oculi muscles. RESULTS: This combined therapy gave good functional and aesthetic results. CONCLUSIONS: The specific causes of blepharospasm and apraxia of lid opening are unknown, but these two conditions coexist in some patients and can be difficult to treat. It is important to make a correct diagnosis, and a combined surgical and botulinum toxin treatment can be very effective.

Visual hallucinations in a case of reversible hypertension-induced brain oedema.

Visual hallucinations are commonly associated with seizures, drug effects, psychiatric disorders, or visual loss as 'release' phenomena. We report the case of a previously healthy 65-year-old woman, who was admitted to hospital with intermittent headache episodes accompanied by complex visual hallucinations. During these episodes the patient's blood pressure was 220/120 mmHg. In between symptomatic episodes she had no complaints and felt healthy. The neurological and ophthalmological examinations were normal but cerebral magnetic resonance imaging (MRI) showed multiple white matter abnormalities in the parieto-occipital regions. Rapid reversal of the symptoms and imaging abnormalities occurred concurrently with lowering of blood pressure. The history and the findings were similar to those recently described in the clinicoradiological 'posterior leukoencephalopathy' syndrome. Different pathogenic mechanisms are discussed. Copyright 1998 Lippincott Williams & Wilkins

Intracranial primary leiomyosarcoma arising in a teratoma of the pineal area.

The case of a 33-year-old man with a primary leiomyosarcoma arising in a mature teratoma in the pineal area is presented. The tumor extended into the posterior part of the third ventricle and caused hydrocephalus. Its smooth muscle derivation was confirmed by immunohistochemistry and electron microscopy. The patient has been followed for more than 2 years after surgery and postoperative radiotherapy. He has full working capacity and there are no signs of tumor recurrence. To our knowledge this is the first presentation of a leiomyosarcoma derived from a teratoma in the pineal area.

Significance of inflammatory changes in the brainstem in forensic autopsy cases.

Brain stem encephalitis is an uncommon disease. In order to assess the significance of inflammatory changes in the brain stem in a forensic autopsy material we reviewed the findings over a 12-year period. Between January 1st 1982-December 31st 1993, neuropathological examination of the brain was carried out in 29% of the autopsy cases from the Institute of Forensic Medicine, University of Oslo. Out of 4546 brains, 110 (2.2%) showed microglial nodules and perivascular lymphocytic cuffing in the lower brain stem. In 66 of the cases (60%), the abnormalities were limited to the nucleus and/or the spinal tract of the fifth cranial nerve. Only 16 of the 39 cases with more widespread changes, diagnosed as brain stem encephalitis, had a serious underlying or concomitant disease. Three particular cases of brain stem encephalitis are reported in more detail. In all three cases we suggest that the brain stem inflammatory changes may be either the direct or a contributory cause of death.

Airway limitation and exercise intolerance in well-regulated myasthenia gravis patients.

OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disease of neuromuscular synapses, characterized by muscular weakness and reduced endurance. Remission can be obtained in many patients. However, some of these patients complain of fatigue. The aim of this study was to assess exercise capacity and lung function in well-regulated MG patients. PATIENTS AND METHODS: Ten otherwise healthy MG patients and 10 matched controls underwent dynamic spirometry, and a ramped symptom-limited bicycle exercise test. Spirometric variables included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximum voluntary ventilation (MVV). Exercise variables included maximal oxygen uptake (VO(2) max), anaerobic threshold (VO(2) AT) maximum work load (W), maximum ventilation (VE max), and limiting symptom. RESULTS: Myasthenia gravis patients had significantly lower FEV1/FVC ratio than controls. This was more marked in patients on acetylcholine esterase inhibitors. On the contrary, patients not using acetylcholine esterase inhibitors had a significantly lower exercise endurance time. CONCLUSION: Well-regulated MG patients, especially those using pyridostigmine, tend to have an airway obstruction. The modest airway limitation might be a contributing factor to their fatigue. Patients who are not using acetylcholinesterase inhibitor seem to have diminished exercise endurance in spite of their clinically complete remission.

Neuropathological changes in ten cases of neuronal intermediate filament inclusion disease (NIFID): a study using alpha-internexin immunohistochemistry and principal components analysis (PCA).

Ten cases of neuronal intermediate filament inclusion disease (NIFID) were studied quantitatively. The alpha-internexin positive neurofilament inclusions (NI) were most abundant in the motor cortex and CA sectors of the hippocampus. The densities of the NI and the swollen achromatic neurons (SN) were similar in laminae II/III and V/VI but glial cell density was greater in V/VI. The density of the NI was positively correlated with the SN and the glial cells. Principal components analysis (PCA) suggested that PC1 was associated with variation in neuronal loss in the frontal/temporal lobes and PC2 with neuronal loss in the frontal lobe and NI density in the parahippocampal gyrus. The data suggest: 1) frontal and temporal lobe degeneration in NIFID is associated with the widespread formation of NI and SN, 2) NI and SN affect cortical laminae II/III and V/VI, 3) the NI and SN affect closely related neuronal populations, and 4) variations in neuronal loss and in the density of NI were the most important sources of pathological heterogeneity.

The course of cervical dystonia and patient satisfaction with long-term botulinum toxin A treatment.

In 78 patients with idiopathic cervical dystonia (CD), we studied the course of the disease and the patients' satisfaction with long-term botulinum toxin A (BTX) treatment (median 5.5 years, range 1.5-10). On a seven-point scale ranging from excellent to worsening, the effect of treatment was scored as excellent or good by 52% of patients and moderate by 33%. The independent scores of the treating neurologists were excellent or good in 65% and moderate in 27%, respectively, and correlated well with the patients' scores. The 'Global Burden of Disease', as expressed on Visual Analog Scales (VAS, 0-10) before and at evaluation of treatment, was reduced by a median of 4 in individual patients. By combining these outcome measures, 67% of the patients were characterized as having a good effect, and 33% an unsatisfactory effect. This outcome (good or unsatisfactory effect) was independent of the severity of head deviation or complexity pattern of CD prior to treatment, the delay from onset to start of BTX treatment, or the number of treatments. The complexity pattern remained stable during treatment in 64% of the patients, became less complex in 19%, whereas 17% of the patients developed more complex patterns.

[Visual hallucinations in ophthalmological and neurological diseases]. / Visuelle hallusinasjoner ved oftalmologiske og neurologiske sykdommer.

Visual hallucination can be defined as visual sensory perception without external stimulation, or something that a patient sees that other observers in the same environment do not see. The images may be unformed (lights, streaks, flashes) or formed (objects, people, scenes). Clinical experience indicates that, despite the infrequency with which they are mentioned, visual hallucinations commonly occur in patients with ophthalmological and neurological diseases. Content, duration and timing of visual hallucinations relate to their cause and provide useful clinical information. This paper reviews the topical, pathophysiological and clinical aspects of visual hallucinations.

The ophthalmology of internal carotid artery dissection.

PURPOSE: Carotid dissection is an important cause of cerebral and retinal ischemic symptoms, especially in young adults. This article presents a patient material and also includes a review of the ophthalmologic signs and symptoms of carotid dissection. MATERIAL AND METHODS: Twenty-eight patients with spontaneous dissection of the extracranial internal carotid artery dissection underwent a neuro-ophthalmological examination. RESULTS: Twenty-three patients had oculosympathetic paresis. Two experienced transient monocular blindness; in one the episodes were provoked by sitting up from a supine position. One patient presented with a monocular visual field defect, due to posterior ischemic neuropathy, and two others with homonym hemianopia. Diplopia, caused by an incomplete VIth cranial nerve palsy was recognised in one. CONCLUSION: All but one patient presented with detectable ophthalmologic symptoms or signs. Very often the ophthalmologist is the first medical contact for patients with internal carotid artery dissection. The condition is serious, and a prompt evaluation and treatment is indicated to prevent irreversible sequelae.