[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.

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.

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.

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.

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.

[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.

[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.

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.

Fatigue in myasthenia gravis: is it more than muscular weakness?

BACKGROUND: Few studies have focused on fatigue in myasthenia gravis (MG), and fatigue in relation to the autonomic system has never been systematically explored in these patients. The study aimed to document the prevalence of MG-related fatigue in ethnic Norwegians and to examine whether MG severity is associated with symptoms of autonomic disturbance, which in turn is associated with fatigue and functional disability. METHODS: Eighty two of the 97 who fulfilled the study inclusion criteria participated in the study. Controls were 410 age- and sex-matched subjects drawn from a normative sample (n = 2136) representative of the Norwegian population. Bivariate analyses and multivariate linear regression analyses were used to assess associations between questionnaire-reported MG severity, symptoms of autonomic disturbance, fatigue (mental and physical) and functional disability. RESULTS: Forty-four per cent (36/82) of patients fulfilled the criteria for fatigue compared with 22% (90/410) of controls (odds ratio 2.0; p = 0.003). Twenty-one per cent of patients (17/82) met the criteria for chronic fatigue versus 12% (48/410) of controls (odds ratio 1.96; p = 0.03). MG patients had higher total fatigue scores than controls (p < 0.001) and a high prevalence of autonomic symptoms, especially poor thermoregulation and sleep disturbance. According to multivariate analyses controlled for MG score, symptoms of autonomic disturbances were independently positively associated with fatigue (p < 0.001), and fatigue was independently negatively associated with functional level (p < 0.001). CONCLUSION: Norwegian ethnic patients with MG have higher levels of fatigue and a higher prevalence of chronic fatigue than controls, even in patients in full remission. MG severity is highly suggestive to be associated with symptoms of autonomic disturbance, which in turn is associated with fatigue and the level of functional disability.

[Drugs that may trigger or exacerbate myasthenia gravis]. / Medikamenter som kan utløse og forverre myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease causing muscle weakness due to impaired transmission at the neuromuscular junction. MG or a MG-like condition may be triggered or exacerbated by several drugs used for treatment of other diseases. Drugs may interfere with the neuromuscular transmission through several mechanisms, either by affecting pre- or postsynaptic ion channels or by affecting acetylcholinesterase. Based on a literature search in PubMed and the authors' own clinical experiences, we provide an overview focusing on the most frequently used drugs that may exacerbate weakness in patients with MG. In our experience, symptomatic MG-patients who have a generalised disease are especially vulnerable to drug-induced exacerbations, while stable MG patients with few symptoms more seldom are. Nevertheless, patients with MG must receive treatment for co-existing conditions. It is important to be aware of a possible increase in muscle weakness when introducing a new drug. If the patient deteriorates, the new treatment must be withdrawn or the dose reduced.

An unusual case of the syndrome of cervical rib with subclavian artery thrombosis and cerebellar and cerebral infarctions.

BACKGROUND: Cerebellar and cerebral infarctions caused by the syndrome of cervical rib with thrombosis of subclavian artery are very unusual. CASE PRESENTATION: We report the case of a 49-year-old male patient with a right cervical rib compression leading to subclavian arterial thrombosis and both cerebellar and cerebral infarctions secondary to retrograde thromboembolisation. Follow-up imaging revealed partial resolution of the thrombosis after combined anti-coagulant and anti-platelet therapy. The cervical rib and first costa were surgically removed to prevent additional events. CONCLUSION: Cervical rib vascular compression should be promptly diagnosed and treated in order to avoid further complications, including cerebrovascular ischemic events.

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.

[Neurofibromatosis type 2 and auditory brainstem implantation]. / Nevrofibromatose type 2 og auditorisk hjernestammeimplantat.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a rare and severe autosomal dominant disorder caused by mutations in a tumour suppressor gene. This article reviews NF2 and its treatment with auditory brainstem implantation. MATERIAL AND METHODS: The review is based on the authors' experience with the disease and literature identified through a non-systematic search of PubMed. RESULTS: NF2 is caused by loss-of-normal function of the tumour suppressor protein merlin. Merlin normally suppresses cell growth and proliferation. The clinical picture is dominated by neurological symptoms, caused by multiple tumours - mainly schwannomas and meningeomas. The hallmark of the disease is development of bilateral vestibular schwannomas, and the most common presenting symptom in adults is progressive hearing loss. Presenile cataract, ocular motility disorders, peripheral neuropathy and skin tumours are other common findings. The majority of patients become deaf, many patients become severely disabled and life expectancy is reduced. The goal of management is conservation of function and maintenance of quality of life. Auditory brainstem implants stimulate the cochlear nucleus directly and provide substantial auditory benefits to patients with NF2. INTERPRETATION: A multidisciplinary approach in specialty centres is recommended. Management by an experienced team reduces mortality and improves outcome after surgery. Auditory brainstem implantation is an important part of the hearing rehabilitation in these patients. Emerging knowledge of the molecular disease mechanisms offers hope for new therapeutic strategies.

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.

[Primary and secondary dystonias]. / Primaere og sekundaere dystonier.

BACKGROUND: Dystonia is a neurological syndrome, characterized by involuntary muscle contractions causing twisting, repetitive movements and abnormal postures. The aim of this brief review is to summarize the current state of knowledge as to the clinical, genetic, diagnostic and therapeutic aspects of dystonia. MATERIAL AND METHODS: This article is based on own research, clinical experience and recent medical literature found by searching Medline. RESULTS AND INTERPRETATIONS: Dystonia is the third most prevalent movement disorder in humans and is a common term for a group of primary (idiopathic) and secondary (symptomatic) movement disorders. For the primary types, tremor and myoclonus are the only symptoms in addition to the dystonia itself. Some primary dystonias have a hereditary component. Secondary dystonias are associated with other diseases with hereditary, metabolic, traumatic or exogen causes. There is still no curative treatment of dystonia, but new therapeutic methods increase the possibility of reducing involuntary movement, abnormal postures and pain, as well as improving function and quality of life for patients with dystonia.

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.