Klaus Hansen

Late-onset myasthenia not on the increase: a nationwide register study in Denmark, 1996-2009.

An increase in late‐onset myasthenia gravis (MG) has been reported. There are few large population‐based studies over longer periods of time reflecting recent developments in MG incidence.

Late onset of stroke-like episode associated with a 3256C→T point mutation of mitochondrial DNA

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are usually associated with the common 3243A-->G mutation of mtDNA. Onset of stroke-like episodes usually occurs before age 30. We report a patient with late onset MELAS harboring a rare 3256C-->T mutation in the tRNA(Leu(UUR)) gene of mtDNA. The patient presented with a stroke-like episode at age 36. MRI showed a stroke-like lesion in the right parietooccipital brain region. Proton MR spectroscopy showed elevated lactate concentrations in the lesion (8.4 mmol/l), and in the mid-occipital region (2.3-3.2 mmol/l) that appeared normal on MRI. Further tests revealed evidence of a severe oxidative defect of muscle metabolism as well.

1H MR spectroscopy of gray and white matter in carbon monoxide poisoning.

Carbon monoxide (CO) intoxication leads to acute and chronic neurological deficits, but little is known about the specific noxious mechanisms. 1H magnetic resonance spectroscopy (MRS) may allow insight into the pathophysiology of CO poisoning by monitoring neurochemical disturbances, yet only limited information is available to date on the use of this protocol in determining the neurological effects of CO poisoning. To further examine the short-term and long-term effects of CO on the central nervous system, we have studied seven patients with CO poisoning assessed by gray and white matter MRS, magnetic resonance imaging (MRI) and neuropsychological testing. Five patients suffered from acute high-dose CO intoxication and were in coma for 1–6xa0days. In these patients, MRI revealed hyperintensities of the white matter and globus pallidus and also showed increased choline (Cho) and decreased N-acetyl aspartate (NAA) ratios to creatine (Cr), predominantly in the white matter. Lactate peaks were detected in two patients during the early phase of high-dose CO poisoning. Two patients with chronic low-dose CO exposure and without loss of consciousness had normal MRI and MRS scans. On follow-up. five of our seven patients had long-lasting intellectual impairment, including one individual with low-dose CO exposure. The MRS results showed persisting biochemical alterations despite the MRI scan showing normalization of morphological changes. In conclusion, the MRS was normal in patients suffering from chronic low-dose CO exposure; in contrast, patients with high-dose exposure showed abnormal gray and white matter levels of NAA/Cr, Cho/Cr and lactate, as detected by 1H MRS, suggesting disturbances of neuronal function, membrane metabolism and anaerobic energy metabolism, respectively. Early increases in Cho/Cr and decreases of NAA/Cr may be related to a poor long-term outcome, but confirmation by future studies is needed.

Serosurvey for antibodies to Borrelia burgdorferi in Danish dogs

To estimate the regional presence of B. burgdorferi we performed a serosurvey for antibodies to B. burgdorferi in 205 healthy dogs from representative areas of Denmark. Blood samples were collected from November 1986 to March 1987. Twenty dogs bred for research purposes served as negative controls. IgG‐antibodies to the B. burgdorferi strain DK‐ECM 1 were measured by indirect immunofluorescens assay. Antibody titers ranged from nonreactive to 640. In 33 dogs (16.1%) titres were ≥80, indicating exposure to B. burgdorferi. There were no significant differences in the prevalence rate of seropositive dogs due to place of residence, sex or age. The results indicate that dogs are exposed to tickborne B. burgdorferi in most areas of Denmark.

Use of azathioprine for non‐thymoma myasthenia and risk of cancer: a nationwide case–control study in Denmark

To evaluate the association between the use of azathioprine and risk of cancer in patients with non‐thymoma myasthenia gravis (MG) in a nationwide setting.

Risk of non-melanoma skin cancer in myasthenia patients treated with azathioprine.

The association between use of azathioprine and risk of non‐melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a nationwide setting. Treatment of autoimmune myasthenia frequently involves long‐term exposure to immunosuppressants, including azathioprine. Use of azathioprine increases the risk of NMSC in organ recipients and probably also in patients with other autoimmune disorders. No previous study has specifically investigated the risk of NMSC in myasthenia patients treated with azathioprine.

Myasthenia and risk of cancer: a population-based case–control study

To evaluate the association between having non‐thymoma myasthenia and the risk of extra‐thymic cancer in a population‐based setting.

Cerebral hyperperfusion syndrome remains under-recognized

We read with interest the report by Kearny et al. [1] entitled ‘‘Autoimmune encephalopathy presenting as a ‘posterior circulation stroke’’. Herein, the authors present a 73-year-old woman with acute onset of aphasia and right arm weakness with a normal CT of the brain 12 h after admission. Diffusion-weighted magnetic resonance imaging (DW MRI) 2 days later showed increased signal in the left hippocampus, amygdala, and the pulvinar region of the thalamus. Symptoms improved over 1 month. The patient received a diagnosis of ‘posterior circulation stroke’ but this was subsequently changed to ‘autoimmune encephalitis’ when she developed steroid-responsive encephalopathy and seizures 1.5 months later. Having identified high voltage-gated potassium channel antibody (VGKC abs) levels, the authors concluded that this was the first reported case of VGKC abs-positive limbic encephalitis with a stroke-like onset. Whereas we have no doubt that the patient indeed fulfilled the diagnostic criteria for VGKC abs-associated encephalitis in the later stage, we also believe that her initial history rather suggests a different diagnosis. First, the DW MRI changes in the mesial temporal lobe cannot explain the aphasia and right arm weakness. These deficits are compatible with a middle artery, not a posterior circulation, syndrome. Second, the authors state that the patient developed aphasia and right arm weakness 5 days after endarterectomy for a high-degree left carotid artery stenosis. Although no further clinical details are provided, this presentation and the lack of relevant findings on the CT and DW MRI are highly suggestive of cerebral hyperperfusion syndrome (CHS). CHS is a rare but well-described entity in patients after carotid endarterectomy or carotid angioplasty with stenting. Patients may present with headache (often ipsilateral to the site of intervention), confusion, and decreased consciousness, as well as focal neurological deficits and seizures corresponding to the vascular territory of the recanalized artery. CHS can be monosymptomatic and short-lived or, if associated with complications such as intracerebral hemorrhage, fatal [2, 3]. Whereas carotid angioplasty with stenting is associated with development of CHS within a few hours, CHS following carotid endarterectomy typically peaks around the sixth postoperative day as in the present patient [3]. Elevated systemic blood pressure, impairment of cerebral autoregulation, and disruption of the blood–brain barrier are believed to provoke reperfusion injury [2, 4]. As reported in another recent issue of the Journal of Neurology, CT (and MRI) brain perfusion shows elevated regional tissue perfusion and thereby assists in differentiating CHS from postoperative transitory cerebral ischemia [5]. CHS is best prevented by firm periand postprocedural blood pressure control. Treatment apart from lowering of blood pressure is mainly supportive according to standard neurointensive care protocols including, if necessary, lowering the intracranial pressure, evacuating intracranial hematoma, and providing antiepileptic drugs [2, 3]. However, awareness of CHS is the key to diagnosis and treatment. We therefore provide this commentary in order to stress the point that CHS remains under-recognized.

Clinical Reasoning: Partial Horner syndrome and upper right limb symptoms following chiropractic manipulation

A 60-year-old man with no medical history was admitted to the Department of Neurology with drooping of his right upper eyelid and an ipsilateral contracted pupil, combined with pain, weakness, and numbness in his upper right limb.

Long term survival, health, social functioning, and education in patients with European Lyme neuroborreliosis: nationwide population based cohort study

Abstract Objective To estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population. Design Nationwide population based cohort study using national registers. Setting Denmark. Participants All Danish residents diagnosed during 1986-2016 as having Lyme neuroborreliosis (n=2067), defined as a positive Borrelia burgdorferi intrathecal antibody test and a clinical diagnosis of Lyme borreliosis, and a comparison cohort from the general population matched on sex and date of birth (n=20u2009670). Main outcome measures Mortality rate ratios, incidence rate ratios of comorbidities, and differences in educational and social outcomes. Results Mortality among patients with Lyme neuroborreliosis was not higher than in the general population (mortality rate ratio 0.90, 95% confidence interval 0.79 to 1.03). Lyme neuroborreliosis patients had increased risk of haematological (incidence rate ratio 3.07, 2.03 to 4.66) and non-melanoma skin cancers (1.49, 1.18 to 1.88). At diagnosis, Lyme neuroborreliosis patients had slightly higher employment and lower disability pension rates. After five years, patients and comparison cohort members had similar numbers of hospital contacts (difference −0.22, 95% confidence interval −0.45 to 0.02, in-hospital days/year; 0.37, −0.10 to 0.83, outpatient visits/year), employment rates (difference 1.5%, −2.1% to 5.1%), income (difference −1000, −20u2009000 to 18u2009000, Danish kroner), days of sick leave (difference −0.3, −3.5 to 3.0, per year), rates of receipt of a disability pension (difference −0.9%, −3.2% to 1.3%), and number of children (difference –0.10, −0.27 to 0.08). More patients were married (difference 4.8%, 2.2% to 7.4%) and had completed high school education (difference 7%, 1% to 12%). Conclusion A verified diagnosis of Lyme neuroborreliosis had no substantial effect on long term survival, health, or educational/social functioning. Nevertheless, the diagnosis decreased labour market involvement marginally and was associated with increased risk of haematological and non-melanoma skin cancers.