POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy.
We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum.
The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations.
POLG1; MELAS; Red-ragged fibers; Stroke-like
Thrombolysis is strongly recommended for patients with significant neurologic deficits secondary to acute ischemic stroke. Extracranial bleeding is a rare but major complication of thrombolysis.
A 78-year-old woman presented with acute ischemic stroke caused by occlusion of the basilar artery. Clinical recovery was observed after successful recanalization by intravenous thrombolysis and intraarterial thrombectomy. However, the patient complained of sudden abdominal pain following the intervention and a newly developed abdominal wall mass was found. CT scan and selective angiography confirmed active bleeding from the left epigastric artery into the abdominal muscle layer and the bleeding was successfully managed by selective embolization of the bleeding artery.
We report a rare case of abdominal wall hemorrhage after thrombolysis for acute ischemic stroke. The findings indicate that abdominal wall hemorrhage should be considered as a differential diagnosis in the presence of abdominal discomfort after thrombolysis for acute ischemic stroke.
Abdominal wall hemorrhage; Extracranial hemorrhage; Thrombolysis
We report a female patient with familial Creutzfeldt-Jakob disease with V180I mutation (fCJD with V180I), who was serially followed up with magnetic resonance imaging (MRI) and electroencephalogram (EEG) for up to four years.
At 6 months after the onset, diffusion-weighted images (DWI) and fluid-attenuated inversion recovery (FLAIR) of brain MRI revealed an increased signal intensity in the bilateral frontal, temporal, and parietal cerebral cortex with left dominancy except for the occipital lobe. However, her follow-up MRI at four years showed the high-signal regions spreading to the occipital cerebral cortex in DWI and FLAIR images, and bilateral frontal cerebral white matter in FLAIR images. EEG showed a progressive and general slow high-voltage rhythm from 7–8 to 3–5 c/s over four years, without evidence of periodic synchronous discharge. These findings correspond to the symptom progression even after akinetic mutism at 18 months.
We suggest that serial MRI and EEG examinations are useful for early diagnosis of fCJD with V180I and for monitoring disease progression.
Familial Creutzfeldt-Jakob disease; V180I; Magnetic resonance imaging; Electroencephalogram
The autophagic vacuolar myopathies (AVM) are a group of inherited myopathies defined by the presence of autophagic vacuoles in pathological muscle specimens. AVM can be categorized into three groups: acid maltase deficiency, myopathies characterized by autophagic vacuoles with unique sarcolemmal features, and rimmed vacuolar myopathies (RVM). While the pathogeneses of these conditions are still being elucidated, some drugs (e.g., chloroquine, its analog, hydroxychloroquine, and colchicine) can also cause AVM. Minocycline is a disease-modifying anti-rheumatic drug that may be used in the treatment of rheumatoid arthritis (RA). Here, we describe the first case of minocycline-associated AVM with rimmed vacuole formation.
A 75-year-old woman suffering from RA has been continuously treated with minocycline (200 mg/day) for the past 7 years. During this time, she developed a myopathy that predominantly affected her lower limbs. Histological studies of biopsied muscle revealed scattered atrophic myofibers with rimmed vacuoles that contained pigment granules. Histochemical staining revealed that the pigment comprised both iron and melanin, which is consistent with type II minocycline-induced cutaneous pigmentation. Under electron microscopy, autophagic vacuoles were consistently observed in association with numerous collections of pigment granules.
This is the first report of minocycline-induced pigmentation in skeletal muscle. The strong association between autophagic vacuoles and the accumulation of minocycline-induced pigments suggest that long-term minocycline treatment induced pigment accumulation, leading to elevation of autophagic activity and RVM. It might also be possible that minocycline directly activated autophagy, as the observed pigments are known to form complexes containing minocycline and/or its metabolites. As long-term minocycline treatment is expected to be used more widely in the future, we must draw attention to this adverse effect.
Minocycline; Autophagic vacuole; Rimmed vacuolar myopathy; Minocycline-induced pigmentation; Rheumatoid arthritis
Ischemic stroke by septic embolism occurs primarily in the context of infective endocarditis or in patients with a right-to-left shunt and formation of a secondary cerebral abscess is a rare event. Erosion of pulmonary veins by a pulmonary abscess can lead to transcardiac septic embolism but to our knowledge no case of septic embolic ischemic stroke from a pulmonary abscess with secondary transformation into a brain abscess has been reported to date.
We report the case of a patient with a pulmonary abscess causing a septic embolic cerebral infarction which then transformed into a cerebral abscess. After antibiotic therapy and drainage of the abscess the patient could be rehabilitated and presented an impressive improvement of symptoms.
Septic embolism should be considered as cause of ischemic stroke in patients with pulmonary abscess and can be followed by formation of a secondary cerebral abscess. Early antibiotic treatment and repeated cranial CT-scans for detection of a secondary abscess should be performed.
Kikuchi Fujimoto disease (KFD), or histiocytic necrotising lymphadenitis, is a benign and self-limiting condition characterised by primarily affecting the cervical lymph nodes. Recurrent aseptic meningitis in association with KFD is extremely rare and remains a diagnostic challenge.
We report a 28-year-old man who presented 7 episodes of aseptic meningitis associated with KFD over the course of 7 years. Histopathological findings of enlarged lymph nodes led to the diagnosis of KFD. The patient’s headache and lymphadenopathy spontaneously resolved without any sequelae.
A diagnosis of KFD should be considered when enlarged cervical lymph nodes are observed in patients with recurrent aseptic meningitis. A long-term prognosis remains uncertain, and careful follow-up is preferred.
Recurrent aseptic meningitis; Kikuchi-Fujimoto disease; Histiocytic necrotising lymphadenitis; SLE
Adrenomyeloneuropathy (AMN) is one of several phenotypes of the adrenoleukodystrophy spectrum caused by mutations in the ABCD1 gene on the X chromosome. An inflammatory component is part of the disease complex ranging from severe childhood CNS demyelination to spinal cord and peripheral nerve degeneration.
We present a patient with clinical progressive AMN and severe lower limb pain. Longitudinal brain magnetic resonance spectroscopy showed a constant slightly elevated myoinositol/total creatine ratio during the five year treatment period, probably reflecting demyelination, microglial activation and gliosis, indicating an inflammatory response. The pain was refractory to conventional therapy but intravenous immunoglobulin (IVIG) treatment was highly efficient.
IVIG may be considered as a last resort for treatment of refractory pain in AMN patients with indications of an inflammatory component.
Adrenomyeloneuropathy; Limb pain; IVIG treatment; Magnetic resonance spectroscopy
This article reports a rare case of active neurosyphilis in a man with mild to moderate dementia and marked hippocampal atrophy, mimicking early onset Alzheimer’s disease. Few cases have so far described bilateral hippocampal atrophy mimicking Alzheimer’s disease in neurosyphilis.
The patient presented here is a 33 year old Bulgarian male, whose clinical features include progressive cognitive decline and behavioral changes over the last 18 months. Neuropsychological examination revealed mild to moderate dementia (Mini Mental State Examination score was 16/30) with impaired memory and attention, and executive dysfunction. Pyramidal, and extrapyramidal signs, as well as dysarthria and impairment in coordination, were documented. Brain magnetic resonance imaging showed cortical atrophy with noticeable bilateral hippocampal atrophy. The diagnosis of active neurosyphilis was based on positive results of the Venereal Disease Research Laboratory test/Treponema pallidum hemagglutination reactions in blood and cerebrospinal fluid samples. In addition, cerebrospinal fluid analysis showed pleocytosis and elevated protein levels. High-dose intravenous penicillin therapy was administered. At 6 month follow up, improvements were noted clinically, on neuropsychological examinations, and in cerebrospinal fluid samples.
This case underlines the importance of early diagnosis of neurosyphilis. The results suggest that neurosyphilis should be considered when magnetic resonance imaging results indicate mesiotemporal abnormalities and hippocampal atrophy. Neurosyphilis is a treatable condition which requires early aggressive antibiotic therapy.
Neurosyphilis; Dementia; Hippocampal atrophy; Alzheimer’s disease; Magnetic resonance imaging (MRI)
Levetiracetam (LEV) is an antiepileptic drug with a favorable tolerability and safety profile with little or no effect on liver function.
Here, we reported an epileptic pediatric patient who developed a significant elevation in serum alkaline phosphatase level (ALP) during LEV monotherapy. Moreover, the serum ALP level was surprisingly decreased to normal after LEV discontinuation. The Naranjo Adverse Drug Reaction Probability Scale score was 6, indicating firstly LEV was a probable cause for the increased serum ALP.
Cautious usage and concerns of the LEV-associated potential ALP elevation should be considered when levetiracetam is prescribed to epilepsy patients, especially pediatric patients.
Levetiracetam; Serum alkaline phosphatase; Hepatotoxicity; Antiepileptic drugs; Epilepsy
Human cytomegalovirus (CMV) is an ubiquitous pathogen capable of modulating the host immune system. Immune dysfunction is common during CMV infection and includes autoimmune phenomena. Here we focus on a case of primary CMV infection associated with encephalopathy in a patient with a rudimentary spleen. We discuss diagnostic challenges and immunological aspects as well as the hypothesis that CMV may break tolerance and induce potentially encephalitogenic autoantibodies.
A 33-year-old woman was admitted with features of encephalitis, rapidly progressing into a catatonic state. The patient tested negative for presence of herpes simplex virus DNA in cerebrospinal fluid (CSF), and had elevated liver enzymes and hepatomegaly at computed tomography scan (CT) examination. CT scan and magnetic resonance imaging (MRI) showed only a rudimentary spleen. Initially, serum was negative for anti-CMV IgM, but borderline for anti-CMV IgG by enzyme-linked immunosorbent assay. However, a more sensitive assay resulted in a positive specific IgM Western blot profile and low IgG avidity, suggesting primary CMV infection. Further, CMV DNA was retrospectively detected in a CSF sample collected at admission. We also detected antineuronal autoantibodies, which stained GAD-positive neurons in the hippocampus. The patient was treated by a combination of prednisone, intravenous immunoglobulins (IVIg) and antivirals, which resulted in a dramatic amelioration of the patient’s neurological status. One year after admission the patient exhibited a nearly complete recovery with mild deficits in attention and memory.
A possible reason for the critical course of CMV infection could be the lack of a functional spleen in this patient, a condition previously associated with severe CMV infection. Prompt treatment with antiviral drugs, steroids and IVIg was most likely important for the positive outcome in this case and should be considered for similar cases of severe primary CMV infection associated with immunopathological phenomena.
Human cytomegalovirus; Encephalitis; Antineuronal autoantibodies
CADASIL is an autosomal dominant genetic leukoencephalopathy linked to mutations in the Notch3 gene. In rare cases, widespread brain lesions on T2 MRI mimicking multiple sclerosis are observed. From a national registry of 268 patients with adult-onset leukodystrophy, we identified two patients with an atypical presentation of CADASIL without co-occurrence of another systemic disease.
Patient 1 experienced progressive gait disability and patient 2 relapsing optic neuritis and sensory-motor deficit in the leg. Both patients responded to corticotherapy and patient 2 was also responsive to glatiramer acetate. No oligoclonal bands were found in the CSF, and MRI showed myelitis and lesions with gadolinium enhancement in brain (patient 1) or incomplete CADASIL phenotype (patient 2).
In rare cases, an inflammatory-like process can occur in CADASIL. In these patients, immunomodulatory treatments, including corticosteroids, could be effective.
CADASIL; Multiple sclerosis; Leukoencephalopathy; Notch3; Cerebral vasculitis
The diagnosis of transient ischemic attack (TIA) based on clinical history and objective findings, even including multiparametric MRI, can be misleading. We report two patients who presented with TIA-like deficits with isolated perfusion lesions in corresponding areas but were finally diagnosed as transient neurological symptoms associated with dural arteriovenous fistula (dAVF).
Two patients presented with transient focal neurological symptoms lasting less than one hour. An isolated perfusion deficit with no diffusion change in the clinically relevant area was shown on brain MRI, indicating transient ischemia as the most plausible cause of neurological symptoms. However, cerebral angiography let to diagnosis of dAVF in both cases. Intracerebral hemorrhage occurred after the initial diagnosis of TIA in one patient, and the small area of perfusion abnormality accompanied by the enlarged cortical vein in the other case helped to identify the dAVF through the further investigation. The pattern of perfusion-weighted imaging in both cases revealed increase of mean transit time and relative cerebral blood volume denoting the venous congestion in a clinically corresponding area.
Reported cases are uncommon clinical presentation of a dAVF, which can be misdiagnosed as TIA on clinical grounds. In rare cases, the isolated perfusion deficits could be attributable to venous congestion, despite the similar pattern of clinical presentation, such as with TIA.
Transient ischemic attack; Perfusion-weighted imaging; Dural arteriovenous fistula; Magnetic resonance imaging; Transient ischemic attack mimics; Intracerebral hemorrhage
The autosomal dominant spinocerebellar ataxias (SCAs) confine a group of rare and heterogeneous disorders, which present with progressive ataxia and numerous other features e.g. peripheral neuropathy, macular degeneration and cognitive impairment, and a subset of these disorders is caused by CAG-repeat expansions in their respective genes. The diagnosing of the SCAs is often difficult due to the phenotypic overlap among several of the subtypes and with other neurodegenerative disorders e.g. Huntington’s disease.
We report a family in which the proband had rapidly progressing cognitive decline and only subtle cerebellar symptoms from age 42. Sequencing of the TATA-box binding protein gene revealed a modest elongation of the CAG/CAA-repeat of only two repeats above the non-pathogenic threshold of 41, confirming a diagnosis of SCA17. Normally, repeats within this range show reduced penetrance and result in a milder disease course with slower progression and later age of onset. Thus, this case presented with an unusual phenotype.
The current case highlights the diagnostic challenge of neurodegenerative disorders and the need for a thorough clinical and paraclinical examination of patients presenting with rapid cognitive decline to make a precise diagnosis on which further genetic counseling and initiation of treatment modalities can be based.
Spinocerebellar ataxia type 17; Dementia; Short CAG repeat expansion
Post-stroke mania is an infrequent complication after stroke, and the mechanisms underlying this disorder remain unclear. Although a contralesional release phenomenon has been implicated in post-stroke mania, empirical findings are lacking.
We present a case report of post stroke mania. Single photon emission tomography (SPECT) was performed twice, during the manic state and during the remitted euthymic state. The first SPECT study performed during the manic state demonstrated hypoperfusion in the right temporal and frontal regions due to right putaminal hemorrhage. It also showed hyperperfusion in the inferior lateral prefrontal lobe, the temporal lobe, and the medial and lateral parts of the parietal lobe in the left hemisphere. The second SPECT study performed during the euthymic state demonstrated moderate improvement in the hypoperfusion in the right fronto-temporal regions. Furthermore, compared to the findings on the first SPECT study, the second study showed that the focal hyperperfusion in the anterior insular cortex, inferior lateral prefrontal lobes, and superior-middle temporal gyrus in the left hemisphere had vanished.
Increased left inferior prefrontal and anterior insular activity and reduced extensive right fronto-temporal lobe activity are involved in the development of post-stroke mania.
Contralesional release phenomenon; Insula; Mania; SPECT; Stroke
Lymphocyte-depleted Hodgkin’s lymphoma is the rarest form of classical Hodgkin’s lymphoma, accounting for < 1% of all cases. Patients often have advanced-stage disease at the time of presentation with an aggressive clinical course. Even more uncommon is primary extranodal disease and rarely it will be presenting with spinal cord compression.
An 88-year-old Caucasian female presented with a history of upper back pain for several months and new onset bilateral leg numbness and weakness. MRI of the spine showed a dorsal epidural lesion with cord compression at T1-T4 with involvement of the paraspinal muscles. The patient received urgent surgical decompression, with final histopathology showing a lymphocyte-depleted Hodgkin’s lymphoma. Systemic work-up did not show evidence of nodal disease. Following surgery, she received a course of radiotherapy with good outcome.
To the best of our knowledge, this is the first reported case of primary lymphocyte-depleted Hodgkin lymphoma presenting as epidural spinal cord compression. Our report, in conjunction with a review of the literature, suggests that surgical intervention is clearly indicated in de novo disease followed by radiotherapy.
Spinal cord compression; Primary; Lymphocyte-depleted Hodgkin’s lymphoma
Cerebellar and cerebral infarctions caused by the syndrome of cervical rib with thrombosis of subclavian artery are very unusual.
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.
Cervical rib vascular compression should be promptly diagnosed and treated in order to avoid further complications, including cerebrovascular ischemic events.
Subclavian artery/pathology; Cervical Rib syndrome/complications; Arterial thoracic outlet syndrome; Stroke/complications
Alzheimer’s disease (AD) is the most common form of dementia. Mutations in genes such as those encoding amyloid precursor protein (APP), presenilin 1 and presenilin 2, are responsible for early-onset familial AD.
In this study, we report a 275341 G > C (Val717Leu) mutation in the APP gene in a Japanese family with early onset AD by genetic screening. This mutation has previously been detected in European families. In the Japanese family we screened, the age at onset of AD was 47.1 ± 3.1 years old (n = 9; range, 42–52). The symptoms in the affected members included psychiatric vulnerability and focal signs such as pyramidal signs, epileptic seizures, and myoclonic discharges. An MR imaging study showed relatively mild atrophic changes in the bilateral hippocampus and cerebral cortices in all affected members compared with their clinical presentations.
We conclude that the clinical features of Alzheimer’s disease can be different even when caused by the same mutation in the APP gene. Further clinical and genetic studies are required to clarify the relationship between phenotypes and genotypes.
Kleine-Levin syndrome is a rare sleep disorder of unknown etiology. It is characterized by intermittent periods of excessive sleepiness, cognitive disturbances and behavioral abnormalities. Nine cases of familial Kleine-Levin syndrome have been identified, but there are no reported cases describing twins that are affected by the syndrome.
We report the cases of 16-year-old monozygotic twin boys who both suffered from Kleine-Levin syndrome. In both cases, the onset of the first episode was preceded by an influenza infection. During symptomatic periods they slept for the entire day except for meals and bathroom visits. Actimetry recordings revealed that during symptomatic periods, daily activity was lower than that of asymptomatic periods, on the other hand, activity during the night was significantly higher in symptomatic periods than asymptomatic periods. Polysomnography (PSG) data during symptomatic periods revealed a decrease in sleep efficiency. Human leukocyte antigen (HLA) typing revealed no DQB1*02 loci. They were administered lithium carbonate but the beneficial effect was limited.
Our observations suggest that Kleine-Levin syndrome may be due to genetic and autoimmune processes, although etiologic relationship to specific HLA type remains controversial.
Recurrent hypersomnia; Kleine-Levin syndrome; Monozygotic twins; HLA typing; Polysomnography; Actimetry
Distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy is clinically characterized by the early involvement of distal leg muscles. The striking pathological features of the myopathy are muscle fibers with rimmed vacuoles. To date, the role of aquaporin-4 water channel in distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy has not been studied.
Here, we studied the expression of aquaporin-4 in muscle fibers of a patient with distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy. Immunohistochemical and immunofluorescence analyses showed that sarcolemmal aquaporin-4 immunoreactivity was reduced in many muscle fibers of the patient. However, the intensity of aquaporin-4 staining was markedly increased at rimmed vacuoles or its surrounding areas and in some muscle fibers. The fast-twitch type 2 fibers were predominantly involved with the strong aquaporin-4-positive rimmed vacuoles and TAR-DNA-binding protein-43 aggregations. Rimmed vacuoles with strong aquaporin-4 expression seen in the distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy patient were not found in control muscles without evidence of neuromuscular disorders and the other disease-controls.
Aquaporin-4 might be crucial in determining the survival or degeneration of fast-twitch type 2 fibers in distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy.
Distal myopathy with rimmed vacuoles (DMRV)/hereditary inclusion body myopathy (hIBM); Rimmed vacuoles (RVs); Aquaporin-4 (AQP4); Fast-twitch type 2 fiber