[Myopathy in a patient during simvastatin and fluconazole treatment].

A 69-year-old female was admitted due to progressive loss of muscle strength following addition of fluconazole to long-term simvastatin treatment. Rhabdomyolysis was suspected and both drugs were discontinued. Forced diuresis was initiated together with a short course of prednisolone. After 21 weeks the patient had regained normal muscle strength and endurance. The favourable course and the absence of antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase suggest that the condition was due to interaction between the two drugs, which are both metabolized via the CYP3A4 pathway.

Paraneoplastic Choreoathetosis in a Patient with Small Cell Lung Carcinoma and Anti-CRMP5/CV2: A Case Report.

INTRODUCTION: The occurrence of more or less monosymptomatic paraneoplastic choreoathetosis associated with anti-CRMP5/CV2 antibodies is rare. Typically, such autoantibodies are associated with a more classical syndrome - paraneoplastic encephalomyelitis. Frequently, small cell lung carcinoma (SCLC) is the related neoplastic finding. CASE REPORT: We present a 71-year-old woman who developed visual symptoms with papilledema and chorea. Anti-CRMP5/CV2 antibodies were a feature of both the serum and cerebrospinal fluid. Although SCLC was suspected already at the time of the initial examinations, no signs of primary or metastatic tumors were revealed on chest X-ray, MRI or whole-body PET scan. EEG and bronchoscopy were also unremarkable. However, 6 months after the onset, a repeated PET scan and subsequent bronchoscopic biopsy revealed SCLC. In spite of chemotherapy, the SCLC progressed, and the patient died 14 months after the onset of the symptoms. CONCLUSION: We report paraneoplastic choreoathetosis associated with anti-CRMP5/CV2 antibodies. Such published case histories are rare. Although expected, we did not find any reduced signal intensity at the basal ganglia on the T1-weighted or increased intensity on the T2-weighted MRI scans.

Mortality in myasthenia gravis: A nationwide population-based follow-up study in Denmark.

INTRODUCTION: In previous studies of myasthenia gravis (MG), increased mortality has been reported. The aim of this study was to estimate mortality in patients with acetylcholine receptor antibody-positive (AChR-Ab-seropositive) MG in a nationwide population-based, long-term follow-up study. METHODS: All AChR-Ab-seropositive MG patients, diagnosed between 1985 and 2005, were identified. Defined by age at diagnosis (≤ 50 or >50 years), patients were classified as having early- or late-onset MG. For comparison, 10 non-MG individuals from the general population were matched with each patient. All patients and controls were followed until January 1, 2009. Mortality rates and estimated mortality rate ratios (MRRs) were calculated. RESULTS: Of 702 AChR-Ab-seropositive MG patients, 302 died during follow-up. Overall mortality was higher for patients with MG (MRR = 1.41, range 1.24-1.60). In late-onset women and men, the MRRs were 1.64 (1.36-1.99) and 1.22 (1.02-1.46), respectively. Total MRR was highest during the first 5 years after diagnosis. CONCLUSIONS: MG diagnosis is still associated with increased mortality.

[Workup and treatment of autoimmune encephalitis]. / Udredning og behandling afautoimmun encephalitis.

Autoimmune encephalitis with antibodies against neuronal surface antigens is diagnosed with increasing frequency in recent years. If treated early and aggressively, these conditions often respond favourably to immunotherapy. We describe the clinical features, diagnosis and treatment of the two most common types of autoimmune encephalitis with antibodies against the N-methyl-D-aspartate receptor or the leucine-rich glioma-inactivated 1 protein. Together, these two conditions comprise 80% of the autoimmune encephalitis cases diagnosed in Denmark. Autoimmune encephalitides with rare antibodies are also summarized.

[Autoimmune synaptic encephalitis is a disease entity on the rise]. / Autoimmun synaptisk encefalitis er en underdiagnosticeret sygdomsgruppe.

The term autoimmune synaptic encephalitis (ASE) comprises encephalitides associated with autoantibodies against structures of the neuronal synapse. We review four types of ASE (anti-N-methyl-D-aspartate receptor encephalitis, anti-α-amine-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor encephalitis, anti-gamma-aminobutyric acid receptor 1 encephalitis and anti-leucine-rich glioma-inactivated 1 encephalitis) including their epidemiology, clinical characteristics and treatment.

[Autoimmune synaptic encephalitis]. / To danske tilfælde af autoimmun synaptisk encefalitis.

Autoimmune synaptic encephalitis (ASE) is a recently recognized disease entity. The early and correct diagnosis of ASE is of importance, since the prognosis depends on the early onset of treatment. We present two Danish case reports of ASE: a 15-year-old boy presenting with a severe course of N-methyl-D-aspartate-encephalitis including persistent cognitive deficits, and a 59-year-old woman with coeliac disease presenting with leucine-rich glioma inactivated 1-encephalitis including dyskinesia, epilepsy, psychiatric features and vocal tics.

Behavioral, pharmacological, and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disorders.

Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders.

Identification of continuous epitopes of HuD antibodies related to paraneoplastic diseases/small cell lung cancer.

HuD antibodies are associated with small cell lung cancer. To identify relevant epitopes of HuD antibodies, patient sera and a monoclonal antibody were analyzed for their reactivity to linear 20mer peptides spanning the human HuD protein. The HuD monoclonal antibody recognized a single fragment located in the first RNA recognition motif. Thorough analysis identified VRDKITQGSL as the actual epitope. Screening of anti-HuD positive patients and healthy controls identified eight peptides as potential subdominant epitopes. The majority of these peptides were located in the N-terminal end as well as in the linker region between the second and third RNA recognition motifs.

Increasing incidence of late-onset anti-AChR antibody-seropositive myasthenia gravis.

The incidence of myasthenia gravis (MG) from 1970 through 1999 was studied in an area with 2.3 million inhabitants. The mean annual incidence rate of early-onset MG was constant at 3.5 x 10(-6). In late-onset MG, the rate increased from 4.7 to 20.8 x 10(-6). The two onset types of MG may thus be distinct disorders. The author hypothesized that late-onset nonthymoma anti-acetylcholine receptor antibody-seropositive MG may be provoked by environmental factors.

The occurrence of anti-titin antibodies and thymomas: a population survey of MG 1970-1999.

OBJECTIVE: To estimate the incidence of elevated anti-titin antibodies titers and of thymomas in a population of patients with MG using various statistics and associations. METHODS: Extensive epidemiology, systematic measurement of anti-titin antibodies, and histologic assessment of thymomas according to the new World Health Organization classification. RESULTS: The mean annual incidence rate of MG per million population was 8.3. The analogous mean rate of thymomas was 2.0, out of which MG was encountered in about 20%. A thymoma was coexistent in 7% of the patients with MG. The finding of titin autoantibodies and the coexistence of thymomas were both associated with age at the appearance of MG. In patients with MG with a thymoma, the frequency of seropositivity was 68%, whereas acetylcholine receptor (AChR) autoantibodies were detected in all such sera. Titin autoantibody-positive sera were also anti-AChR antibodies positive. Further, all serum samples negative for anti-AChR antibodies were devoid of anti-titin antibodies. Titin autoantibodies were not detected in nonthymoma early-onset MG. CONCLUSION: Apart from MG with a thymoma, the finding of the titin autoantibodies was observed to be an exclusive feature of late-onset MG, the frequency being 55%. No data were found to suggest that patients with MG were more likely to present with thymic tumors than other patients exhibiting thymic neoplasia. In about 80%, such tumors in MG were composed of cortical cells. The concept of the anti-titin antibodies merely as a paraneoplastic marker in MG was not supported by these data.