Visuell snø ­ forstyrrende, men ufarlig.

Visual snow is a persistent visual disturbance in which small dots of light appear across the visual field of both eyes, like snowfall. The condition is not widely known, but an increasing number of cases have been described in the last 5 - 6 years. Many patients have consulted a number of specialists without receiving an explanation for their symptoms, and in this clinical review article we therefore wish to make the condition known to more clinicians.

[Visual impairment in Parkinson's disease]. / Synsvansker ved Parkinsons sykdom.

Parkinson's disease is characterised by the core motor symptoms: bradykinesia, rigidity and tremor. The disease also has a number of non-motor symptoms, such as visual impairment. Patients may experience blurred vision, sensitivity to light, difficulties in reading, and a subjective feeling of rapid eye fatigue. The visual impairments also affect the patients' motor skills, as vision compensates for poor postural control and difficulty initiating movement. It is important to identify common but frequently underdiagnosed visual impairment, and initiate measures that can increase quality of life and pattern of movement. In this clinical review we present the most common visual impairments in Parkinson's disease, as well as providing advice for improved visual function.

Mutations in the J domain of DNAJB6 cause dominant distal myopathy.

Eight patients from five families with undiagnosed dominant distal myopathy underwent clinical, neurophysiological and muscle biopsy examinations. Molecular genetic studies were performed using targeted sequencing of all known myopathy genes followed by segregation of the identified mutations in the affected families using Sanger sequencing. Two novel mutations in DNAJB6 J domain, c.149C>T (p.A50V) and c.161A>C (p.E54A), were identified as the cause of disease. The muscle involvement with p.A50V was distal calf-predominant, and the p.E54A was more proximo-distal. Histological findings were similar to those previously reported in DNAJB6 myopathy. In line with reported pathogenic mutations in the glycine/phenylalanine (G/F) domain of DNAJB6, both the novel mutations showed reduced anti-aggregation capacity by filter trap assay and TDP-43 disaggregation assays. Modeling of the protein showed close proximity of the mutated residues with the G/F domain. Myopathy-causing mutations in DNAJB6 are not only located in the G/F domain, but also in the J domain. The identified mutations in the J domain cause dominant distal and proximo-distal myopathy, confirming that mutations in DNAJB6 should be considered in distal myopathy cases.

A man in his fifties with variable weakness and difficulty in walking. / En mann i 50-årene med varierende kraftsvikt og gangvansker.

BACKGROUND: An active man in his fifties was treated for atrial fibrillation with ablation. One week later he noticed variable weakness in his lower extremities. In the days that followed, his symptoms improved but could vary from day to day. CASE PRESENTATION: On admission 3 months after the initial symptoms, he had spasticity and weakness in both lower extremities, with hyperreflexia and positive Babinski. Spinal fluid contained slightly elevated protein levels. Spinal MRI showed cord oedema and gadolinium enhancement over multiple spinal levels. Autoimmune myelitis was suspected, and he was treated with high dose steroids and rituximab. Due to lack of effect, repeated examinations were initiated. Information from his patient history regarding symptom exacerbation by walking or bending forward was emphasised. Repeated MRI showed unchanged spinal oedema and dilated peri- and intramedullary vessels. MRA and spinal digital DSA revealed a dural fistula at third lumbar level, with the left L3 radiculomedullary artery as the feed artery. The fistula was successfully ligated by the neurosurgeon. INTERPRETATION: Spinal vascular lesions are rare and the diagnosis may be challenging due to atypical presentation. The case shows that detailed information from the patient history and thorough clinical investigation is of paramount importance to disclose this probably underreported condition.

Atypisk optikusnevritt.

Typical optic neuritis is a demyelinating inflammation of the optic nerve, often associated with multiple sclerosis and with a relatively good prognosis. A small percentage of optic neuritis cases have divergent clinical characteristics and a different underlying aetiology. These atypical cases of optic neuritis must be treated more intensively and followed up more closely in order to preserve visual function. It is important to be aware of the atypical features, so that correct assessment and treatment is initiated.

Neurodegenerative Interplay of Cardiovascular Autonomic Dysregulation and the Retina in Early Multiple Sclerosis.

Introduction: Autonomic nervous system (ANS) symptoms are prevalent in multiple sclerosis (MS) as is neurodegeneration. Our aim was to explore the occurrence of ANS symptoms and retinal neurodegeneration in a newly diagnosed MS population with tools available in a clinical setting. Methods: Forty-three MS patients and 44 healthy controls took part in the study. We employed a bedside cardiovascular ANS test battery together with classical pupillometry, optical coherence tomography (OCT) evaluation of retinal neurodegeneration in eyes without previous optic neuritis (MSNON) and patients' self-report forms on fatigue, orthostatic and ANS symptoms. Results: Half of the patients presented with ANS symptoms and a high level of fatigue. There was a significant difference in ganglion cell layer thickness (mean GCIPL) evaluated by OCT in MSNON compared to healthy control eyes. We found a negative linearity of mean GCIPL on group level with increasing disease duration. Three patients fulfilled the criteria of postural orthostatic tachycardia syndrome (POTS). Conclusion: Our results demonstrate retinal neurodegeneration in MSNON, a high frequency of fatigue and a high prevalence of ANS symptoms in newly diagnosed patients. Whether neurodegeneration precedes ANS dysfunction or vice versa is still open to debate, but as unveiled by the presence of POTS in this MS population, differences in stress-response regulation add to the understanding of variation in onset-time of ANS dysfunction in early MS.

A teenager with acute bilateral visual loss. / En tenåring med akutt bilateralt synstap.

BACKGROUND: The diagnosis of acute optic neuropathy is made clinically. In young patients demyelinating optic neuritis is the most common cause. However, other autoimmune diseases, infections and other non-inflammatory conditions may also cause inflammation. Careful clinical workup is necessary to establish the correct diagnosis and treatment. We describe the clinical approach to a case of acute optic neuropathy with several atypical features. The same case was published in the Journal of Neuro-Ophthalmology. CASE PRESENTATION: A male teenager developed acute and painless bilateral visual loss. Fundoscopy revealed optic disc hypaeremia with telangiectasia. Magnetic resonance imaging demonstrated contrast enhancement of the optic nerves and chiasm without evidence of demyelinating disease. There was no visual improvement after methylprednisolone treatment. Genetic analysis for the 3 common Leber hereditary optic neuropathy (LHON) mutations was negative. However, idebenone treatment was followed by a marked improvement in visual function. Whole mitochondrial genome sequencing eventually detected a rare LHON mutation. INTERPRETATION: There are many different causes of acute optic neuropathy. Making the correct diagnosis is important, as clinical management differs. Idebenone is now a treatment option for LHON. Whole mitochondrial genome sequencing is sometimes necessary to confirm the diagnosis.

ULTRA-WIDE-FIELD FUNDUS IMAGING IN THE DIAGNOSIS AND FOLLOW-UP OF SUSAC SYNDROME.

PURPOSE: To present the use of ultra-wide-field (UW) fundus imaging in the diagnosis and follow-up of a patient with Susac syndrome. METHODS: Case report of a myopic patient presenting initially with rhegmatogenous retinal detachment. A significant portion of the retina was found to be avascular bilaterally at presentation. Surgery was performed with scleral buckle. Then, UW color and autofluorescent imaging and UW fluorescein angiography were obtained. RESULTS: Successful retinal reattachment was obtained. Enlargement of the avascular area with neovascularization was observed at eight-month follow-up. In addition, the patient presented severe neurosensory hearing loss and clinical depression postoperatively. The results of UW fluorescein angiography revealed hyperfluorescent macular spots, arteriolar wall hyperfluorescence, leakage from retinal neovascularization, and confirmed the avascularity of two thirds of the retina, whereas the results of UW autofluorescence showed absence of the normal hypofluorescent retinal vessels outside the posterior pole. Findings of UW imaging in combination with systemic involvement led to the diagnosis of Susac syndrome. Appropriate treatment stopped the disease progress, ameliorated symptoms, and some of the occluded retinal vessels were reperfused. CONCLUSION: In conclusion, UW fundus imaging is a valuable modality in the diagnosis and follow-up of patients with Susac syndrome. Early diagnosis and treatment is critical, particularly as it can lead to reperfusion of occluded retinal vessels.

Fatigue and cognition: Pupillary responses to problem-solving in early multiple sclerosis patients.

INTRODUCTION: In early multiple sclerosis (MS) patients, cognitive changes and fatigue are frequent and troublesome symptoms, probably related to both structural and functional brain changes. Whether there is a common cause of these symptoms in MS is unknown. In theory, an altered regulation of central neuropeptides can lead to changes in regulation of autonomic function, cognitive difficulties, and fatigue. Direct measurements of central neuropeptides are difficult to perform, but measurements of the eye pupil can be used as a reliable proxy of function. METHODS: This study assesses pupil size during problem-solving in early MS patients versus controls. A difference in pupil size to a cognitive challenge could signal altered activity within the autonomic system because of early functional brain changes associated with cognitive load. We recruited MS patients (mean disease duration: 2.6 years, N = 41) and age-matched healthy controls (N = 43) without eye pathology. Neurological impairment, magnetic resonance imaging, visual evoked potentials, depression, and fatigue were assessed in all of the patients. In both groups, we assessed processing speed and retinal imaging. Pupil size was recorded with an eye-tracker during playback of multiplication tasks. RESULTS: Both groups performed well on the cognitive test. The groups showed similar pupillary responses with a mean of 0.55 mm dilation in patients and 0.54 mm dilation in controls for all the tasks collapsed together. However, controls (N = 9) with low cognitive scores (LCS) had an increased pupillary response to cognitive tasks, whereas LCS MS patients (N = 6) did not (p < .05). There was a tendency toward a smaller pupillary response in patients with fatigue. CONCLUSIONS: This is the first study to investigate pupillary responses to cognitive tasks in MS patients. Our results suggest that MS-related changes in cognition and fatigue may be associated with changes in arousal and the autonomic regulation of task-related pupillary responses. This supports the theory of a link between cognition and fatigue in MS.

[Idiopathic intracranial hypertension as a cause of headache]. / Idiopatisk intrakranial hypertensjon.

Idiopathic intracranial hypertension (IIH) is characterised by increased intracranial pressure with normal cerebrospinal fluid, and no evidence of space occupying process, meningeal pathology or venous thrombosis. The condition is associated with obesity, especially in women of childbearing age. IIH is a rare but serious cause of headache, and constitutes a differential diagnosis for sudden-onset headache, particularly if the patient has visual disturbances not related to migraine and reports pulsatile tinnitus, cranial nerve palsy or radiculopathy.

Severe inflammatory disease activity 14 months after cessation of Natalizumab in a patient with Leber's optic neuropathy and multiple sclerosis - a case report.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) co-occuring with multiple sclerosis-like disease (LHON-MS) is suggested to be a separate disease entity denoted Harding's disease. Little is known about the response to initiation and discontinuation of potent immunomodulatory treatment in LHON-MS. CASE PRESENTATION: We describe a LHON-MS patient with 27 years disease duration who developed severe disease activity peaking 14 months after discontinuation of natalizumab, with extensive new inflammatory lesions throughout the brain and in the spinal cord resembling immune inflammatory reconstitution syndrome. She had previously been clinically and radiologically stable on natalizumab treatment for 6 years, and before that only experienced subtle clinical activity during 9 years on interferon beta1a. CONCLUSION: This is the first report on severe exacerbation of inflammatory disease activity after discontinuation of natalizumab in LHON-MS, and suggests that late rebound activity can occur in these patients.

[Myasthenia gravis - optimal treatment and accurate diagnosis]. / Myasthenia gravis - diagnostikk og behandling.

Around 700 people in Norway have myasthenia gravis, an autoimmune disease that affects neuromuscular transmission and results in fluctuating weakness in some muscles as its sole symptom. The diagnosis is based on typical symptoms and findings, detection of antibodies and neurophysiological examination. Symptomatic treatment with acetylcholinesterase inhibitors is generally effective, but most patients also require immunosuppressive drug treatment. Antigen-specific therapy is being tested in experimental disease models.

Eye and hand motor interactions with the Symbol Digit Modalities Test in early multiple sclerosis.

PURPOSE: Eye and hand motor dysfunction may be present early in the disease course of relapsing-remitting multiple sclerosis (RRMS), and can affect the results on visual and written cognitive tests. We aimed to test for differences in saccadic initiation time (SI time) between RRMS patients and healthy controls, and whether SI time and hand motor speed interacted with the written version of the Symbol Digit Modalities Test (wSDMT). METHODS: Patients with RRMS (N = 44, age 35.1 ± 7.3 years), time since diagnosis < 3 years and matched controls (N = 41, age 33.2 ± 6.8 years) were examined with ophthalmological, neurological and neuropsychological tests, as well as structural MRI (white matter lesion load (WMLL) and brainstem lesions), visual evoked potentials (VEP) and eye-tracker examinations of saccades. RESULTS: SI time was longer in RRMS than controls (p < 0.05). SI time was not related to the Paced Auditory Serial Addition Test (PASAT), WMLL or to the presence of brainstem lesions. 9 hole peg test (9HP) correlated significantly with WMLL (r = 0.58, p < 0.01). Both SI time and 9HP correlated negatively with the results of wSDMT (r = -0.32, p < 0.05, r = -0.47, p < 0.01), but none correlated with the results of PASAT. CONCLUSIONS: RRMS patients have an increased SI time compared to controls. Cognitive tests results, exemplified by the wSDMT, may be confounded by eye and hand motor function.

Pseudoperipheral palsy: a case of subcortical infarction imitating peripheral neuropathy.

BACKGROUND: Vascular damage in the central hand knob area can mimic peripheral motor nerve deficits. CASE PRESENTATION: We describe the case of a woman presenting with apparent peripheral neuropathy. Brain magnetic resonance imaging and computed tomography angiography revealed an infarct in the precentral hand knob area, with significant stenosis in the right proximal middle cerebral artery trunk. Subsequent 3-Tesla magnetic resonance imaging of the brain suggested cerebral angiitis. The patient experienced improved hand function following combined glucocorticoid and cyclophosphamide treatment. CONCLUSION: Vascular damage in the hand knob area should be considered when evaluating peripheral motor nerve deficits in the presence of normal nerve conduction velocities. The diagnosis of cerebral angiitis remains a major challenge for clinicians.

[Posterior cortical atrophy]. / Posterior kortikal atrofi.

BACKGROUND: Posterior cortical atrophy is a neurodegenerative condition with atrophy of posterior parts of the cerebral cortex, including the visual cortex and parts of the parietal and temporal cortices. It presents early, in the 50s or 60s, with nonspecific visual disturbances that are often misinterpreted as ophthalmological, which can delay the diagnosis. The purpose of this article is to present current knowledge about symptoms, diagnostics and treatment of this condition. METHOD: The review is based on a selection of relevant articles in PubMed and on the authors' own experience with the patient group. RESULTS: Posterior cortical atrophy causes gradually increasing impairment in reading, distance judgement, and the ability to perceive complex images. Examination of higher visual functions, neuropsychological testing, and neuroimaging contribute to diagnosis. In the early stages, patients do not have problems with memory or insight, but cognitive impairment and dementia can develop. It is unclear whether the condition is a variant of Alzheimer's disease, or whether it is a separate disease entity. There is no established treatment, but practical measures such as the aid of social care workers, telephones with large keypads, computers with voice recognition software and audiobooks can be useful. INTERPRETATION: Currently available treatment has very limited effect on the disease itself. Nevertheless it is important to identify and diagnose the condition in its early stages in order to be able to offer patients practical assistance in their daily lives.

A de novo Mutation in the SCN4A Gene Causing Sodium Channel Myotonia.

We describe the case of a six year old boy with findings consistent with myotonia congenita: muscular hypertrophy, stiffness when commencing movements and typical warm-up signs. The most prominent symptom was myotonia of the eyelid muscles with apparent swelling around the eyes. Even though the pronounced warm-up phenomena in our patient suggested a chloride channel-associated myotonia congenita, the myotonia of his eyelid muscles indicated an involvement of sodium channels. Screening for mutations in the underlying CLCN1 gene was negative, however, in the SCN4A gene, we identified the missense mutation c.2108T>C; p.Leu703Pro for which there is strong evidence of pathogenicity because it arose de novo in the index patient.

Overnight response to infliximab in neurosarcoidosis: a case report and review of infliximab treatment practice.

OBJECTIVES: Central nervous system manifestations of sarcoidosis occur in approximately 5% of patients with sarcoidosis, often lead to substantial morbidity, and therefore require immediate treatment. Spinal cord involvement is exceptionally rare. The tumor necrosis factor-α inhibitor infliximab seems to be an effective alternative in severe cases, refractory to other therapies, but a standard concept of treatment is lacking. METHODS: We presented a case of severe corticosteroid-refractory spinal cord sarcoidosis with immediate and dramatic response to infliximab. In addition, we reviewed the literature on infliximab therapy in neurosarcoidosis and drew parallels to other medical fields in order to have a basis for decision making in the initiation and discontinuation of treatment. RESULTS: We identified a total of 34 case reports on effective infliximab treatment of therapy-resistant neurosarcoidosis through PubMed search. Nineteen of the 34 cases reported the duration until treatment response. In accordance with our patient, 14 of the 34 case reports showed improvement between first and third infusion. Eight of the 34 cases reported sustained remission after cessation of infliximab. No definite treatment regimen was used. CONCLUSIONS: Infliximab seems to be a fast-acting and effective drug for severe neurosarcoidosis. No systematic treatment strategy is available because of lack of controlled trials. Until then, therapy regimens may be adapted to those used in other medical fields where infliximab treatment is well established.