A patient with a benign course of neuromyelitis optica (Devic's syndrome) over 12 years: MRI follow up and histological findings.
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Adult↗
Biomedical subjects
E Neuen-Jacob
Publications and source records attributed to E Neuen-Jacob.
Coenzyme Q10 deficiency and isolated myopathy.
Three unrelated, sporadic patients with muscle coenzyme Q10 (CoQ10) deficiency presented at 32, 29, and 6 years of age with proximal muscle weakness and elevated serum creatine kinase (CK) and lactate levels, but without myoglobinuria, ataxia, or seizures. Muscle biopsy showed lipid storage myopathy, combined deficiency of respiratory chain complexes I and III, and CoQ10 levels below 50% of normal. Oral high-dose CoQ10 supplementation improved muscle strength dramatically and normalized serum CK.
Adult↗
[Glycogenesis Type II (M. Pompe). Selective failure of the respiratory musculature--a rare first symptom].
Late-onset Pompe's disease, a generalized lysosomal glycogen storage disease caused by acid maltase deficiency, usually presents as a slowly progressive muscular weakness of proximal muscles in lower limbs, followed by involvement of respiratory muscles. In the case presented here, however, respiratory failure was the first and selective symptom which caused the uncommon appearance of a patient entering our outpatient clinic on foot carrying his own artificial respirator. Intercostal muscle biopsy eventually led to the diagnosis.
Adult↗
CIDP and isolated osteosclerotic myeloma.
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Adult↗
Dopamine deficits and regulation of the cAMP second messenger system in brains of simian immunodeficiency virus-infected rhesus monkeys.
The basal ganglia, structures rich in the neurotransmitter dopamine, are primarily affected during human immunodeficiency virus (HIV) infection. The authors measured levels of dopamine and its metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid, in brains of uninfected and simian immunodeficiency virus (SIV)-infected rhesus monkeys during the asymptomatic stage of the infection. Moreover, the authors investigated changes in cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB), two factors involved in the signaling pathway of dopamine. The brain regions examined were the nucleus accumbens and the corpus amygdaloideum, which are limbic structures of the basal ganglia that are involved in the pathophysiology of psychiatric disorders and substance abuse. Dopamine content was reduced in both regions of SIV-infected monkeys compared to uninfected animals. Moreover, dopamine deficits were associated with a decrease in expression of total CREB. Intracellular concentrations of cAMP were decreased in nucleus accumbens and remained unchanged in corpus amygdaloideum of SIV-infected macaques. Changes in dopamine signaling were not related to pathology or viral load of the investigated animals. The results suggest that dopamine defects precede neurologic deficits and implicate dysfunction of the dopaminergic system in the etiopathogenesis of HIV dementia. Therefore, affective complications in HIV subjects should not be interpreted only as reactive psychological changes. The alterations in the mesolimbic dopaminergic system during asymptomatic stage of SIV infection implicate a biological background for psychiatric disorders in HIV infection.
3,4-Dihydroxyphenylacetic Acid↗
Differential diagnosis of high serum creatine kinase levels in systemic lupus erythematosus.
We report the clinical and bioptic findings for a 57-year-old woman with severe chloroquine-induced myopathy. Since 1989, she had been suffering from systemic lupus erythematosus (SLE) with renal involvement and undergone periods of treatment with azathioprine and cyclophosphamide. Additional therapy with chloroquine (CQ) was started because of arthralgia. At the same time, slightly increased creatine kinase (CK) levels were noted. Myositis was suspected, and the patient was treated with steroids. The CK increase persisted, however, and she developed progressive muscular weakness and muscular atrophy. Routine controls revealed markedly elevated CK levels of 1,700 U/l. The neurological and electrophysiological findings were not typical of myositis. Thus, muscle biopsy of the deltoid muscle was performed in order to exclude polymyositis or toxic myopathy. As it revealed chloroquine-induced myopathy, medication was stopped. Discriminating between primary SLE-induced affection of the musculoskeletal system and drug-induced side effects is important for appropriate treatment of SLE patients.
Antirheumatic Agents↗
Intracerebral neurocysticercosis mimicking glioblastoma multiforme: a rare differential diagnosis in Central Europe.
A 47-year-old Greek man presented with a 4-week history of speech difficulties. CT and MRI revealed a low-density multilobulated cystic frontal mass with peripheral ring contrast enhancement adjacent to the sylvian fissure. Examination was normal. Blood tests revealed leucocytosis (16,000 cells/microl) and an elevated erythrocyte sedimentation rate (30/52). A malignant brain tumour was suspected and surgically removed. Histological examination disclosed intracerebral neurocysticercosis.
Brain Diseases↗
Cricopharyngeal muscle hypertrophy associated with florid myositis.
Hypertrophy of the cricopharyngeal muscle is a serious clinical condition that can cause severe dysphagic symptoms, including prolonged deglutition and postdeglutitive aspiration. Although the therapeutical concepts are well established, the pathogenic mechanism of cricopharyngeal hypertrophy remains unclear. We present a patient with a ten-year history of progressive dysphagia. The neurological and MRI findings were normal. However, videocineradiography showed severe hypertrophy of the cricopharyngeal muscle. This condition was first treated by injections of botulinum toxin, which did not alleviate the symptoms. Next, myotomy and muscle biopsy were performed. Histological evaluation disclosed lymphoplasmacellular florid myositis, single-fiber atrophy, and muscle fiber necrosis with phagocytosis. There were no signs of inclusion body myositis or oculopharyngeal muscular dystrophy. Our finding of severe cricopharyngeal muscle hypertrophy associated with myositis has been published previously (n = 34). The study presented here shows cricopharyngeal dysphagia associated with various systemic diseases, including motor neuron disease, general granulomatous disease, dermatomyositis, or inclusion body myositis. Isolated changes of the cricopharyngeal muscle were described in 65% of the cases.
Aged↗
Glycogenosis type V (McArdle's disease) mimicking atypical myositis.
A 13-year-old girl was referred to our clinic because of a positive rheumatoid factor test, muscle pain and weakness. Laboratory evaluation revealed an increased ESR, hypergammaglobulinaemia, antinuclear antibodies, circulating immune complexes, complement consumption and elevated serum creatine kinase (CK) activity. A needle biopsy of the dolent muscle showed normal routine histology. Immunohistochemistry disclosed single lymphocytes and a weak myocytic HLA class I expression. The diagnosis of myositis was considered and corticosteroids were initiated, leading to an increase of complement levels and a decrease of CK-activity and ESR. She subjectively felt stronger but still reported exercise intolerance and metabolic myopathy was considered. Myophosphorylase activity was completely lacking, establishing the diagnosis of McArdle's disease. CK level was found to be elevated in an obese 4-year-old brother too, who refused extensive walking but reported no muscle pain. Myophosphorylase deficiency was demonstrated by histochemistry and by biochemical analysis of his muscle. The female case illustrates that in children with the clinical picture of inflammatory myopathy and serological but not clinical response to therapy underlying metabolic muscle disorders should be excluded. Since the pathogenesis of polymyositis remains unclear, we speculate that inflammatory changes observed in the muscles may have been initiated by muscular damage resulting from the underlying metabolic disease. The serological changes remained unexplained and may contribute to a so far undeterminable connective tissue disease.
Adolescent↗
Autosomal dominant distal myopathy: further evidence of a chromosome 14 locus.
In 1995 Laing et al. (Am J Hum Genet 56(1995)422) described a single family with nine members affected by an autosomal dominant infantile onset distal myopathy. This family generated a LOD score of 2.6 for a locus on chromosome 14. We describe two families with an infantile onset distal myopathy: a new family with four affected members and the family previously described by Scoppetta et al. (Acta Neurol Scand 92(1955)122) in both of which haplotype segregation was compatible with linkage to the same chromosome 14 locus, generating LOD scores of 0.9 at a penetrance of 100% for the markers D14S283 and D14S64 (theta=0) in both families. The loci for autosomal recessive hereditary inclusion body myopathy and Nonaka myopathy on chromosome 9 and for autosomal dominant distal myopathy of Markesberry-Griggs and Udd on chromosome 2q31-33 were excluded by linkage analysis. The disease followed a uniform course with selective wasting of the anterior tibial muscles, starting in infancy and recognizable by a characteristic clinical sign of the 'hanging big toe'. This was followed by slow progression, with involvement of the finger and wrist extensor muscles in the third decade and proximal limb muscles in the fourth decade. Interestingly, we also found evidence of an accompanying mild peripheral neuropathy in the oldest individual with hypomyelination of numerous large myelinated fibres. In addition, this patient's muscle biopsy also showed autophagic vacuoles and numerous intranuclear tubulo-filamentous inclusions of 15-20 nm diameter. Given that all three families with infantile onset distal myopathy are compatible with linkage to the same locus on chromosome 14, this study supports evidence for, and enlarges the clinical and neuropathological spectrum of the distal myopathy on chromosome 14.
Adolescent↗
Local inflammation and devascularization--in vivo mechanisms of the "bystander effect" in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma.
Somatic gene therapy with the herpes simplex virus type I thymidine kinase gene/ganciclovir (HSV-Tk/GCV) system and murine retroviral vector producer cells (VPCs) was introduced as a new adjuvant treatment modality to treat tumor bulk and to prevent tumor recurrence in patients harboring malignant glioma. The single-center experience after treatment of 27 patients undergoing tumor resection followed by intracerebral VPC injection for HSV-Tk suicide gene therapy will be presented focused on findings of systematic and close MRI follow-up and a few histological specimens. The data indicate that hemorrhagic necrosis due to endothelial cell transfection mediated vessel necrosis and that local inflammatory immune response occurs frequently after gene therapy. These phenomena seem to be specific because none of the patients of a control group showed any similar features. The prognosis (time to progression, survival) of the patients with "bystander effects" after gene therapy was better, but compared to those patients without bystander effects, they were also privileged by a favorable constellation of prognostic factors. Therefore, the appearance of these neuroradiologic features cannot serve as an indicator for treatment effectiveness and outcome.
Adolescent↗
Morphological studies on CLN2.
Electron microscopic, fluorescence microscopic, and immunohistochemical studies earlier performed on archival cerebral tissue from Max Bielchowsky's original three patients revealed curvilinear bodies rich in subunit C of mitochondrial ATP synthase (SCMAS). Recent progress in the elucidation of CLN2, i.e. identification of the defective lysosomal enzyme tripeptidyl-peptidase I (TPP-I) and mutations in the CLN2 gene have further corroborated earlier data. Immunohistochemically the absence of the TPP-I protein could be confirmed in the archival tissues using pathological controls. Unlike biochemistry, immunohistochemistry enables examination of these archival tissues elucidating the causative defect. Complementary molecular studies identified mutations in the CLN2 gene in the archival tissues and thereby convincingly demonstrated that these three children truly had classic late infantile neuronal ceroid lipofuscinosis (LINCL), now called CLN2. This archival study documents the possibilities to revalidate disease-specific original nosologic reports. Chloroquine is toxic to lysosomal enzymes and results in lysosomal storage. The material is autofluorescent and gives the ultrastructural pattern of curvilinear profiles, thus resembling classic late infantile NCL, representing a good experimental model. In humans chloroquine therapy may cause a myopathy (and retinopathy) and, as recently suggested, an encephalopathy marked by lysosomal accretion in several cell types including neurons. Immunohistochemically, SCMAS also accumulates, further strengthening morphologic similarity between LINCL and human chloroquine intoxication.
Aminopeptidases↗
Reducing body myopathy with cytoplasmic bodies and rigid spine syndrome: a mixed congenital myopathy.
At the age of five years a male child started to develop a progressive rigid spine, torsion scoliosis, and flexion contractures of his elbows, knees, hips, and ankles owing to severe proximal and distal muscle weakness. He had three muscle biopsies from three different muscles at ages 7, 11, and 14 years, respectively. Myopathologically, these muscle tissues contained numerous inclusions which, at the ultrastructural level, turned out to be reducing bodies and cytoplasmic bodies, often in close spatial proximity. Similar histological inclusions, although not further identified by histochemistry and electron microscopy, were seen in his maternal grandmother's biopsied muscle tissue who had developed weakness of the legs and hands after the age of 50 years. The patient's parents were healthy, but the mother's quadriceps muscle showed an increased spectrum of muscle fibre diameters. Our patient, thus, had a neuromuscular disorder, perhaps familial, presenting as a mixed congenital myopathy, i.e., reducing body myopathy with cytoplasmic bodies, of which the morphological lesions could be consistently documented over several years in his different limb muscles. While other mixed congenital myopathies had shown cores and rods, both related to sarcomeres and thus possibly morphogenetically related, cytoplasmic bodies thought to be related to Z-bands and reducing bodies dissimilar to any muscle fibre constituent do not share any common denominator. Therefore, we suggest that this neuromuscular disorder may be a unique mixed congenital myopathy, either sporadic or genetic. In the latter case, the transmission pattern suggested X-linked recessive inheritance, but an autosomal-dominant transmission with variable penetrance could not be ruled out.
Adult↗
Changes in canine skeletal muscles during experimental tibial lengthening.
In 24 beagles, lengthening of the right tibia was performed by callus distraction after osteotomy and application of a ring fixator. Distraction was started at the fifth postoperative day, with a distraction rate of 0.5 mm twice per day, and ended after 25 days. A control group of six additional dogs underwent tibial osteotomy and external fixation without distraction. Twelve animals with and three animals without leg lengthening were euthanized immediately after the distraction period of 25 days (Group A); the remaining 15 dogs were euthanized after an additional consolidation phase of another 25 days (Group B). From the distracted right leg and from the left control leg the tibialis anterior muscle, extensor digitorum longus muscle, peroneus longus muscle, and gastrocnemius muscle were removed and studied by means of routine histologic, histochemical, and immunohistochemical analyses, and electron microscopic examination. The muscles of the control group showed no differences between the right and left sides. However, in the other 24 dogs of Groups A and B, the authors saw marked alterations affecting only the lengthened muscles but not the muscles of the control limbs. These changes were highly significant and included muscle fiber degeneration and regeneration, target fibers, central cores, minicores, marked endomysial and perimysial fibrosis, and atrophy of Type 1 and Type 2 fibers. In the consolidation period (Group B) fiber type grouping indicated that reinnervation had occurred. In addition, an increase in satellite cells and myoblasts and proliferation of nuclei were observed. The findings of the current study indicate that leg lengthening results not only in muscle fiber degeneration followed by regeneration and reinnervation but also in formation of new muscle tissue.
Animals↗
Focal myopathy induced by chronic heroin injection is reversible.
We report a patient who developed a focal myopathy with prominent contractures of his thigh muscles induced by chronic heroin injection. Muscle biopsy and magnetic resonance imaging (MRI) were indicative of a fibrotic and inflammatory process. Treatment with steroids, D-penicillamine, and physical therapy led to full functional recovery within 6 months. Sequential electromyographic (EMG) studies and muscle biopsies showed evidence of regenerating muscle fibers and absence of inflammatory cells. We conclude that heroin-induced focal myopathy is reversible and that combination therapy with D-penicillamine and steroids may be useful.
Adult↗
Morphometric analysis of canine skeletal muscles following experimental callus distraction according to the Ilizarov method.
Muscle fiber diameter and fiber-type distribution were analyzed during callus distraction. The right tibia in 24 beagles was lengthened 2.5 cm by callus distraction after osteotomy and application of a ring fixator. Distraction was started at the fifth postoperative day, at a rate of two times for 0.5 mm per day. Twelve dogs that underwent limb-lengthening and three dogs in the control group that did not undergo limb-lengthening were killed at the end of the 25-day distraction phase (group A). The remaining dogs (12 that underwent limb-lengthening and three that did not) were killed after an additional consolidation period of 25 days (group B). The tibialis anterior, extensor digitorum longus, peroneus longus, and gastrocnemius muscles were removed from the right limb (which had undergone distraction) and the left control side of each animal. Crosscut cryostat sections were stained by adenosine triphosphatase at pH 4.3 and 9.4 to determine the size and distribution of types I and II fibers. Morphometric analysis of the muscle fibers was performed by a computer-assisted two-point technique. On the lengthened side, the muscles revealed marked atrophy affecting predominantly type-II fiber in the dogs in group A and affecting both fiber types in dogs in group B. Fiber density increased in both groups. In addition, fiber-type grouping indicative of reinnervation was obvious in group B. Fiber-type distribution in the dogs in group B showed a shift toward type I in the tibialis anterior (p = 0.043) and extensor digitorum longus (p = 0.034) muscles and a shift toward type II in the gastrocnemius (p = 0.038). The data show that tension-stress during tibial lengthening leads to atrophy of type-II fiber, reflecting disuse of muscle fiber in the distraction period as well as neurogenic atrophy followed by the reinnervation processes. Furthermore, the data are consistent with the occurrence of histoneogenesis during limb-lengthening resulting in an increase in fiber density.
Animals↗
Successful treatment of hepatitis B virus associated polyarteritis nodosa with a combination of prednisolone, alpha-interferon and lamivudine.
Therapy of hepatitis B virus (HBV)-associated poly-arteritis nodosa is still evolving. Here we report a successful treatment with a short-term steroid administration in combination with a-interferon and lamivudine and a complete sequence analysis of the HBV genome. A 58-year-old man presented with the symptoms of mononeuritis multiplex associated in time with the onset of highly replicative hepatitis B. Polyarteritis nodosa was confirmed by biopsy. During an initial course with alpha-interferon and prednisolone no clinical improvement or hepatitis B virus seroconversion was observed. After addition of lamivudine to the protocol with fast tapering of prednisolone, HBV DNA fell to undetectable levels within 1 month and liver transaminases normalized. After 6 months of treatment HBeAg seroconversion took place, followed by HBsAg seroconversion 2 months later. Clinical symptoms of polyarteritis improved. No relapse of polyarteritis or hepatitis B was seen during the follow up of 9 months. Complete sequence analysis of the HBV genome revealed 6 nucleotide mutations but none in a relevant antigenic epitope. The present protocol of short-term prednisolone administration combined with alpha-interferon and lamivudine was effective for the treatment of HBV-related polyarteritis nodosa and may be a promising new therapeutic approach.
Antiviral Agents↗
Enlargement of a chronic aseptic lumbar epidural abscess by intraspinal injections--a rare cause of progressive paraparesis.
The frequent use of invasive procedures at the spinal cord such as epidural injections has led to an increased incidence of iatrogenic abscesses. We report the case of a patient who suffered from low back pain. During epidural lumbar injections of steroids the patient developed severe radicular symptoms, resulting in severe paraparesis. We demonstrate the rare cause of this progressive deterioration, being a combination of a preexisting chronic aseptic epidural abscess and an iatrogenic enlargement by repeated epidural injections. MR-Scans demonstrated a mass lesion at the L4/5 vertebral level, which was surgically removed. Histological evaluation revealed the presence of a chronic aseptic spinal epidural abscess with acute bleedings. Histology and MR-Data disclosed multiple deposits of the applied drug within the abscess and in the surrounding paravertebral soft tissue. The authors prove that the cause of the neurological deterioration was due to epidural injections into a preexisting lumbar chronic aseptic epidural abscess. Harmful and unpleasant complications may occur following epidural injections. Though we present a very rare cause of such complications, a careful monitoring of the neurological status of the patient is necessary as well as the early application of MR imaging in the case of deterioration.
Disease Progression↗