Progressive Difficulty In Walking Research Articles

Calcification of the ligamentum flavum in the thoracolumbar spine: an unusual cause of compressive myelopathy

The focal calcification or ossification of the ligamentum flavum is a rare cause of thoracic myelopathy and most often occurs among individuals of Japanese descent. It is rare in other ethnic groups and in individuals below the age of 50. It is most often described at the lower thoracic level, being uncommon in the lumbar region and rare in the cervical region. Here, we present the case of a 44-year-old White female patient who sought medical attention with an eightmonth history of paraesthesia of the lower limbs and progressive difficulty in walking. The clinical profile, together with computed tomography and nuclear magnetic resonance imaging of the spine, led to a diagnosis of compressive thoracic myelopathy due to ossification of the ligamentum flavum in the thoracic and lumbar spine. The patient underwent laminectomy and dissection of some of the affected ligamentum flavum, without any intraoperative complications. After three months of clinical follow-up, the patient had progressed favorably, having no sensory complaints and again becoming ambulatory.

Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency with unknown genetic defect

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessively inherited disorder of fatty acid metabolism due to ETFA, ETFB or ETFDH mutations. Riboflavin treatment ameliorates symptoms and metabolic profile in ETFDH-related MADD patients. We report on a 20-year-old boy with an 8-year history of progressive difficulty in walking, running and climbing stairs. Muscle biopsy showed a lipid myopathy and the acylcarnitine profile analysis was suggestive of MADD. Nevertheless, no evidence of molecular defects in the ETFA, ETFB and ETFDH exons or intron-exon boundaries was found. Treatment with riboflavin for 1 year resulted in a clear improvement in motor functions. Our report shows that some cases of MADD are not linked to ETFA, ETFB and ETFDH exon or intron-exon boundary changes. They could be due to quite rare promoter or deep intronic mutations or, most likely, to some unknown genetic defect. We therefore suggest to extend in these cases molecular studies to cDNA analysis and indicate the need of extensive pedigree studies to identify other possible disease-related loci. Most important, treatment of these cases with riboflavin can also be effective. Therefore, early diagnosis is essential to achieve the best treatment response.

Hipopituitarism due to primary empty sella and uncommon muscular symptoms

Muscular abnormalities are uncommon manifestations of secondary adrenal insufficiency [1]. Herein, an elderly woman with an unusual muscular presentation of hypopituitarism due to empty sella and secondary adrenal insufficiency is described. A 75-year-old woman reported severe pain and contracture in both thighs associated with progressive difficulty in walking for the past three weeks. Response to analgesics and NSAI was limited. Her past medical history was unremarkable. Physical examination showed a wellappearing woman with normal vital signs. There was pronounced stiffness and pain in the aductor muscles of both thighs. Movement of lower extremities was painful. The electromyography did not show abnormal findings. Laboratory test results showed sodium 118 mEq/l, potassium 4.4 mEq/l, creatin-kinase 356 U/l (0‐167), LDH 777 U/l (240‐480), and C-reactive protein 2.0 mg/dl (0‐0.5). An endocrine evaluation was performed due to presence of severe hyponatremia: free T4 \ 0.4 ng/dl (0.93‐1.7), TSH 1.31 mIU/ml (0.27‐4.2), FSH 1.7 mIU/l (26.5‐139), LH 0.4 mIU/l (20‐65), GH \ 0.13 pg/l, and prolactin was normal. At 10 AM, serum cortisol and plasma ACTH levels were 3.5 lg/dl (5‐20) and 29.4 pg/ml (0‐52), respectively. Twenty-four-hour urinary cortisol was 6.0 lg (10‐90). A short ACTH stimulation test showed low serum cortisol response. MRI of the brain revealed an empty sella (Fig. 1). Replacement therapy was started with hydrocortisone and levothyroxine. She has remained well since. Primary empty sella, a rare neuroradiological finding in the general population, has been related to a congenital incomplete formation of the sellar diaphragm resulting in herniation of the subarachnoid space within the sella and increasing the intracranial pressure. Most common symptoms reported as presentation of primary empty sella were headache, visual disturbances, rhinorrea, and endocrine dysfunction [2]. This patient had biochemical evidence of secondary adrenal insufficiency, and endocrinological testing demonstrated secondary adrenal insufficiency and hypopituitarism related to empty sella. The clinical syndrome developed slowly, over several weeks. Patients with slow onset adrenal insufficiency (as this) usually complain of constitutional syndrome, abdominal pain, nausea, and diarrhea. Musculoskeletal abnormalities are a rare presentation of this disease.

Child Neurology: Hereditary spastic paraplegia in children

Because the medical literature on hereditary spastic paraplegia (HSP) is dominated by descriptions of adult case series, there is less emphasis on the genetic evaluation in suspected pediatric cases of HSP. The differential diagnosis of progressive spastic paraplegia strongly depends on the age at onset, as well as the accompanying clinical features, possible abnormalities on MRI, and family history. In order to develop a rational diagnostic strategy for pediatric HSP cases, we performed a literature search focusing on presenting signs and symptoms, age at onset, and genotype. We present a case of a young boy with a REEP1 (SPG31) mutation. A 4-year-old boy presented with progressive walking difficulties from the time he started walking at the age of 12 to 13 months. His family history was significant for minimal gait abnormalities with onset after age 35, occurring in the patient's mother, maternal grandfather, and maternal aunt; none of them had ever sought medical attention. Neurologic examination revealed a mildly spastic gait and marked lower limb hyperreflexia with bilateral Babinski signs present. Vibration perception was reduced at the ankles. Neurologic examination of the patient's mother and maternal aunt revealed subtle gait abnormalities with bilateral Babinski signs present. MRI of the brain and spinal cord and general metabolic screening revealed no abnormalities. Diagnostic genetic testing in both the patient and his mother revealed a pathogenic mutation (c.417 + 1 G>T) in REEP1 (SPG31) which causes a pure HSP. Mutations in ATL1 (SPG3A) and SPAST (SPG4) had previously been excluded. HSP is a genetically and clinically heterogeneous group of disorders in which the main clinical feature is progressive lower limb spasticity secondary to pyramidal tract dysfunction. HSP is classified as pure if neurologic signs are limited to the lower limbs (although urinary urgency and mild impairment of vibration perception in the distal lower …

541 The Diagnosis and Treatment Particularities in a Case with Juvenile Idiopathic Arthritis

Background and aims: To emphasize the diagnosis peculiarities and treatment difficulties in a case with joint pains. Methods: The authors present a 15 year-old girl admitted for chronic limping. Personal history: morning stiffness and progressive walking difficulties due to arthralgia during last 12 months, progressive regression in motor skills. The girl has followed a chronic therapy with retard penicillines because of persistent high ASLO titer (rheumatic fever suspicion). Clinical exam: impaired nutritional status (- 3 SD), symmetric joint involvement: pain and swelling for proximal interphalangeal hand joints, metacarpophalangeal joints, wrists, knees, ankles and temporomandibular joints, boutonniere deformities and ankylosis for hand fingers, hands and legs muscles atrophy. Results: Laboratory investigations: elevated inflammatory markers, negative rheumatoid factor, positive antinuclear antibodies, high ASLO titer, hypergammaglobulinemia. The imagistic approach: periarticular osteoporosis (wrist radiographs), narrowed joint spaces and erosions. Synovial biopsy has revealed suggestive features for juvenile idiopathic arthritis (JIA). According to diagnosis, the treatment has included physical therapy, anti-inflammatory drugs and methotrexate. Even under methotrexate therapy, the joint function has deteriorated with hand fingers progressive ankylosis. The biologic therapy (etanerceptum) has been initiated with improvement of joint mobility, synovial inflammation and osteoporosis, too. Conclusions: The patient was misdiagnosed as rheumatic fever due to high ASLO titers that can be explained by polyclonal and non-selective B lymphocytes activation. In this case, ASLO titer was correlated with disease's activity. The case peculiarity: it's important to consider the JIA diagnosis for cases with persistent high ASLO titers and unresponsiveness to penicillin therapy.

Thoracic spinal cord herniation in a patient with long-standing ankylosing spondylitis

The objective of this study was to describe an adult male patient with ankylosing spondylitis (AS) associated with thoracic spinal cord herniation (TSCH). TSCH is a scarce entity presented as a displacement of thoracic cord through an anterior or anterolateral dural defect. More importantly, the co-occurrence of AS and thoracic spinal cord herniation is exceptional. To date, only one case of SCH in association with AS has been reported in the literature. A 56-year-old male patient presented with the progressive difficulty in walking and numbness of both lower limbs for the past 18months. The patient was diagnosed as AS when he was 30years old. Sagittal MRI of thoracic spine showed dural defect of the posterior aspect of T11 and 12 vertebral bodies. Axial T2-weighted MRI demonstrated that spinal cord was displaced ventrally and to the right. The diagnosis of TSCH with AS was established. The prognosis was explained to the patient. We recommended duraplasty for dural repair to the patient, but he refused surgery. The results demonstrated that TSCH associated with long-standing AS was very uncommon, and MRI is recommended to rule out SCH in the long-standing AS patients with neurologic symptoms. The SCH in AS might be caused by inflammation, and thoracolumbar hyperkyphosis results from AS might be associated with the development of SCH.

Clinically asymptomatic adult patient with extensive LBSL MRI pattern and DARS2 mutations

Leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate (LBSL) is defined by (a) a recessive inheritance, (b) a slowly progressive spinocerebellar syndrome, and (c) signal abnormalities of various tracts on magnetic resonance imaging (MRI) involving the corpus callosum, the pyramidal tracts, the brainstem, the cerebellar peduncles, the mesencephalic trigeminal tract, the cerebellar white matter, and the dorsal columns of the spinal cord [1–3]. LBSL is associated with mutation in the DARS2 gene, encoding for mitochondrial aspartyl-tRNA synthetase (mtAspRS) [4]. We report the first asymptomatic adult patient with a typical MRI aspect of LBSL associated with a new DARS2 mutation. The index case, a 23-year-old French Caucasian woman, without medical or family history, had progressive walking difficulties since the age of four. Clinical examination showed spastic paraparesis, mixed proprioceptive and cerebellar ataxia, and intention tremor in both upper limbs. She was able to walk 500 m without help. Brain and spinal MRI revealed a typical aspect of LBSL (Fig. 1a), and the presence of high lactate levels in the abnormal cerebral white matter on magnetic resonance spectroscopy (MRS). Sequence analysis of the DARS2 gene [4] revealed compound heterozygous mutations, i.e. a 228-16C[G mutation located in the stretch of C residues just upstream of exon 3 and a second novel missense mutation c.745C[A in exon 8 (Fig. 2). To study the deleterious effect of the mutations, we further analysed the first degree relatives of the index case (parents, two brothers of age 30 and 36, and one sister of age 28), after the patient’s written consent was obtained. Clinical examination was strictly normal in all relatives including vibration sense in the lower limbs. Direct genomic sequencing of exons 3 and 8 showed a heterozygote state in the father (c.745C[A mutation), the mother (228-16C[G mutation), and the two brothers (c.745C[A mutation). The 28-year-old asymptomatic sister had heterozygote composite mutations (228-16C[G P. Labauge (&) Department of Neurology, CHU Nimes, Hopital Caremeau, 2 Avenue du Pr Debre, 30029 Nimes Cedex 4, France e-mail: labauge@yahoo.fr

An atypical phenotype of CJD associated with the E200K mutation in the prion protein gene

E200K mutation of the prion protein gene (PRNP) presented with a variety of phenotypes. A 55-year-old woman complaining of slowly progressive walking difficulties came to our observation. She showed a severe progressive ataxo-spastic syndrome but a mild cognitive impairment only. Repeated EEGs showed a diffuse slowing of the rhythm without specificity. Brain MRI revealed by FLAIR showed widespread multiple hyperintensities in the whole cerebral cortex, caudate and putamen nuclei, and in the pulvinar and medial thalamus bilaterally. These signal abnormalities were best detected by DWI with restricted diffusion on ADC map. The clinical diagnosis of possible genetic Creutzfeldt-Jakob disease (CJD) has been confirmed by PRNP gene analysis which revealed the presence of a E200K mutation. This report confirms the heterogeneity of phenotypes in E200K mutated familial CJD with the occurrence of a new phenotype not previously described.

CK elevation and progressive toe walking in a 14-year old girl

We present the case of a 14-year old girl with progressive toe walking and great difficulties in climbing stairs. The neurological exam was remarkable for weakness of the shoulder girdle musculature with bilateral scapula alata, positive Gower's sign, hyperlordosis upon climbing stairs, inability to walk on heels and positive Trendelenburg's sign when walking. Repeated CK levels were in the range of 3500 U/L. A muscle MRI showed fatty degeneration of calf muscles and to a lesser degree of the dorsal thigh musculature on T1 weighted images. Atrophy of dorsal thigh musculature was present. Muscle biopsy of the deltoid muscle was performed. Conventional histology showed modest myopathic alterations with significant variation in fiber size, increase in endo- and perimysial connective tissue and necrosis of type 1 and 2 muscle fibers. Immunostaining of the material was unremarkable. Eventually a form of limb-girdle muscular dystrophy was suspected Sequencing of the calpain-3 gene was performed and confirmed this diagnosis. The genetic analysis found a compound heterozygosity with a deletion in Exon 4 (c.550delA) which is a known founder mutation in Eastern Europe. The other allele carries a novel deletion of exons 11–13 causing the reading frame to shift. As a result of both mutations there is a complete absence of functional calpain-3 protein.

Successful treatment for a patient with esophageal carcinoma that amalgamates with polymyositis: a case report

Polymyositis is known to amalgamate with malignant tumor. Here, we report a case of successfully resected esophageal carcinoma that amalgamated with polymyositis. Moreover, this is a rare case of squamous cell carcinoma combined with Barrett’s adenocarcinoma. A 47-year-old man was admitted to a hospital because of progressive dysphagia and difficulty in walking. Laboratory data showed creatine phosphokinase (CPK) was elevated, and he was diagnosed with polymyositis. He was treated with steroids, and the symptoms were improved with decreased CPK. Endoscopic and pathological examination showed a squamous cell carcinoma (0-Ipl, SM2-3) combined with Barrett’s adenocarcinoma (0-IIa, M2) of the esophagus. Although we were concerned about postoperative complications associated with polymyositis, the postoperative course was good, with decreased steroid, and he was discharged on the 21st postoperative day. At 1.5 years after surgery, he reports no recurrence of polymyositis or esophageal cancer.

Clival dysgenesis associated with Chiari Type 1 malformation and syringomyelia

We report an 11-year-old boy with dysgenesis of the clivus. The boy presented complaining of progressive difficulty in walking. The clival anomaly was associated with severe basilar invagination, Chiari Type 1 malformation and syringomyelia. Our literature search did not reveal any previous reports of this combination of conditions. The patient obtained relief from his symptoms following a foramen magnum decompression.

Teaching Neuro Images : “Penguin” or “hummingbird” sign and midbrain atrophy in progressive supranuclear palsy

An 82-year-old man presented to us with a 2-year history of progressive difficulty walking. On examination, he had bradykinesia, bradyphrenia, …

Guillain-Barré Syndrome with asystole requiring permanent pacemaker: a case report

IntroductionGuillain-Barré syndrome is an acute demyelinating disorder of the peripheral nervous system that results from an aberrant immune response directed at peripheral nerves. Autonomic abnormalities in Guillain-Barré syndrome are usually transient and reversible. We present a case of Guillain-Barré syndrome requiring a permanent pacemaker in view of persistent symptomatic bradyarrhythmia.Case PresentationAn 18-year-old Caucasian female presented with bilateral lower limb paraesthesias followed by bilateral progressive leg weakness and difficulty in walking. She reported an episode of an upper respiratory tract infection 3 weeks prior to the onset of her neurological symptoms. Diagnosis of Guillain-Barré syndrome was considered and a lumbar puncture was performed. Cerebrospinal fluid revealed albuminocytologic dissociation (increased protein but normal white blood cell count) suggestive of Guillain-Barré syndrome and hence an intravenous immunoglobulin G infusion was started. Within 48 hours, she progressed to complete flaccid quadriparesis with involvement of respiratory muscles requiring mechanical ventilatory support. Whist in the intensive care unit, she developed multiple episodes of bradycardia and asystole requiring a temporary pacemaker. In view of the persistent requirement for the temporary pacemaker for more than 5 days, she received a permanent pacemaker. She returned for follow-up three months after discharge with an intermittent need for ventricular pacing.ConclusionGuillain-Barré syndrome can result in permanent damage to the cardiac conduction system. Patients with multiple episodes of bradycardia and asystole in the setting of Guillain-Barré syndrome should be evaluated and considered as potential candidates for permanent pacemaker implantation.

Toxin Induced Continuous Muscle Fiber Activity Syndrome

Continuous Muscle Fiber Activity Syndrome describes rare heterogeneous group of conditions that exhibit sustained, diffuse motor unit activity due to hyperactivity of peripheral nerve motor axons. The disorder, which has both inherited and acquired forms, is characterized by muscular stiffness, cramps, fasciculation and weakness particularly in the limbs. We report a case 42 year old male who presented with easy fatigability and insidious onset gradually progressive difficulty in walking due to muscle stiffness in both lower limbs along with continuous twitching of muscles of all 4 limbs and chin. EMG study showed spontaneous, continuous, irregular rapid discharges of motor-unit potentials. doi: 10.5214/ans.0972.7531.2008.150405 Competing interests: None. Source of Funding: None Received Date: 25 Sept 2008 Revised Date: 15 Oct 2008 Accepted Date: 27 Oct 2008

A multilevel thoracolumbar meningioma in a young woman

Spinal meningiomas of five or more vertebral segment long are very rare and also less common in younger patients. Under 50 years of age these tumors are more commonly genetical and have worse prognosis. A 25-year-old woman presented with back pain and progressive walking difficulty. An intradural extramedullary tumor extending from thoracal 9th to lumbar 2nd vertebral body was detected. The patient was operated and the tumor was totally removed. The histopathological diagnosis was angiomatous meningioma. Neurological symptoms and signs partially improved postoperatively. Interestingly, magnetic resonance imaging of this patient might easily be confused with ependymoma. Although we performed laminectomy and instrumentation, to maintain stability laminoplasty should be the first treatment modality for such a young patient.

Spinal cord involvement during hypertensive encephalopathy: clinical and radiological findings

Sirs: Reversible posterior leukoencephalopathy syndrome (RPLS) during acute hypertension, with oedema in predominantly posterior cerebral areas, is a well-known clinical and radiological event. To date however, no reports have referred to involvement of the spinal cord. We describe a patient with RPLS in association with extensive reversible oedema of the cervical cord. A 44-year-old woman, whose blood pressure (BP) had not been checked for several years, was admitted to our department following a 15-day period of weakness in her lower limbs with progressive difficulty in walking, constipation and urinary urgency, together with headaches, drowsiness and blurred vision. She used oral contraceptives, had two spontaneous miscarriages, and was a heavy smoker. The patient was negative for substance abuse. Neurological examination revealed moderate paraparesis, brisk tendon reflexes, bilateral Hoffmann and plantar extensor response. The patient was slightly disoriented and had severe headaches. Her BP was 240/140 mmHg. Blood tests and CSF examination were normal. Examination of the fundus oculi disclosed hypertensive retinopathy. Brain MRI revealed abnormal high signal intensity localized in the brainstem in fluid-attenuated inversion recovery (FLAIR) sequences, while spinal T2weighted sequences showed extensive hyperintense areas from the craniocervical junction to the 7th vertebra, without contrast enhancement (Fig. 1A, B). Treatment with anti-hypertensive drugs was commenced. Within two weeks, BP had returned to normal and stabilised, and conventional MRI displayed a complete resolution of abnormalities in the cervical cord and nearly complete resolution in the brainstem (Fig. 1C, D). Diffusion-weighted imaging (DWI) was normal. Following consistent improvement of paraparesis, which completely disappeared one month later, the patient was subsequently discharged. At the six-month follow-up, the subject was completely asymptomatic, neurological and MRI findings were normal, and BP had stabilised at normal values following chronic antihypertensive treatment. RPLS, with oedema in the posterior cerebral lobes and brainstem, is a relatively common occurrence in acute hypertensive episodes [1, 2]. In addition to hypertension, RPLS may be related to an endothelial dysfunction induced by underlying conditions including eclampsia, renal failure, cocaine use and immunosuppressive drug therapy. On rare occasions, predominant involvement of the brainstem with relative sparing of the posterior lobes may occur [3]. The pathogenesis of HTE seems to be related to autoregulatory failure resulting in passive overdistension of cerebral arterioles, rather than to vascular spasms as previously assumed. When a sudden, sustained upsurge in BP overwhelms the upper limit of cerebral blood flow autoregulation, it causes segmental vasodilatation, disruption of the blood-brain barrier and extravasation of fluid into the interstitium [4, 5]. The reversibility of lesions observed at MRI follow-up, performed once BP had returned to normal, strongly supports this theory [6], confirming how lesions reflect vasogenic rather than cytotoxic oedema. Ischemic lesions are uncommon in RPLS; indeed, vasogenic oedema are likely capable of irreversibly altering tissue perfusion, causing infarction in surrounding regions, only in very severe cases not receiving prompt treatment. Although studies performed to investigate spinal cord blood-flow regulatory mechanisms are scarce, important experimental results have confirmed the presence of autoregulatory mechanisms throughout the central nervous system [7], thus establishing a clear concordance between vascular dynamics in the brain and spinal cord. Accordingly, as occurs in cerebral blood flow, hypertensive episodes may be capable of altering autoregulation of spinal blood flow. On exceeding the upper limit of autoregulation, reversible vasogenic oedema may also occur in the spinal cord. Moreover, in HTE, the extremely rare observation in the cord of reversible oedema, commonly reported in the brain, suggests a higher sensitivity of the LETTER TO THE EDITORS

Spinal claudication due to myxopapillary ependymoma

Spinal, also called neurogenic, claudication is common, and in the elderly it is almost invariably caused by degenerative disease of the lumbar spine. There are, however, a few rare but...

Progressive myelopathy due to meningeal thickening in shunted patients: description of a novel entity and the role of surgery

Spinal cord compression due to meningeal thickening is a rare occurrence in shunted patients. Because of the long delay to clinical onset, this complication has not been identified as yet. We report on nine cases of shunt-related progressive myelopathy due to meningeal thickening (SPMMT). We reviewed our database of shunted children, for cases having developed progressive tetraparesis due to cervical meningeal thickening. We identified nine observations of SPMMT, eight of these with hydrocephalus due to neonatal meningitis; the last case had Dandy-Walker malformation shunted at birth and suffered postoperative meningitis. The age of clinical onset of myelopathy was between 6 and 20 years (median 12.8). All patients presented with slowly progressive walking difficulties with falls and no spinal pain. Magnetic resonance imaging (MRI) showed typically a thickened dura mater with collapse of the arachnoid space, compensatory expansion of the epidural fat, and T2 hyperintensity in the spinal cord. We operated on seven patients for surgical decompression and arachnoidolysis: One died postoperatively because of shunt malfunction, and two others died later of complications of tetraplegia. Three patients were aggravated after surgery, three experienced partial improvement, but one of these subsequently deteriorated again. SPMMT appears to be a novel and well-defined clinical and pathological entity; its pathological and radiological features are stereotyped; however, the diagnosis is delayed because of the slow pace of the disease. Although surgical decompression may be the only option, its results were poor in our experience; earlier surgery might improve this grim prognosis.

Bovine mucopolysaccharidosis type IIIB

Mucopolysaccharidosis IIIB, an autosomal recessive lysosomal storage disorder of heparan sulfate caused by mutations in the alpha-N-acetylglucosaminidase (NAGLU) gene, was recently discovered in cattle. Clinical signs include progressive ataxia, stumbling gait, swaying and difficulty in balance and walking. These clinical signs are usually first observed at approximately 2 years of age and then develop progressively over the lifespan of the animals. Affected bulls were found to be homozygous for the missense mutation E452K (c.1354G > A). The availability of mutational analysis permits screening for the NAGLU mutation to eradicate this mutation from the cattle breeding population.

Solitary thoracic intradural extramedullary plasmacytoma

The bodies of the vertebrae are common locations for plasma cell diseases such as multiple myeloma and solitary plasmacytoma. Secondary invasion of the epidural space is infrequent but can cause neurological symptoms. Spinal cord compression due to pure intradural plasma cell infiltration is very rare. The authors report a 25-year-old woman who developed a progressive difficulty in walking due to a solitary spinal dural plasmacytoma. This is the first reported example in the English language literature of a purely intradural spinal plasmacytoma in a patient without other myelomatous lesions. An entirely intradural solitary plasmacytoma has a relatively better prognosis.