Search

OPA1 variants most frequently manifest phenotypically with pure autosomal dominant optic atrophy (ADOA) or with ADOA plus. The most frequent abnormalities in ADOA plus in addition to the optic nerve affection include hypoacusis, migraine, myopathy, and neuropathy. Hypertelorism and atrophy of the acoustic nerve have not been reported. The patient is a 48yo Caucasian female with slowly progressive, visual impairment since childhood, bilateral hypoacusis since age 10y, and classical migraine since age 20y. The family history was positive for diabetes (father, mother) and visual impairment (daughter). Clinical examination revealed hypertelorism, visual impairment, hypoacusis, tinnitus, weakness for elbow flexion and finger straddling, and generally reduced tendon reflexes. MRI of the cerebrum was non-informative but hypoplasia of the acoustic nerve bilaterally was described. Visually-evoked potentials revealed markedly prolonged P100-latencies bilaterally. Acoustically-evoked potentials were distorted with poor reproducibility and prolonged latencies. Muscle biopsy revealed reduced activities of complexes I, II, and IV. Genetic work-up revealed the novel variant c.1463G>C in the OPA1 gene. This case provides novel information regarding the genotype of ADOA plus. The novel OPA1 variant c.1463G>C not only manifests with visual impairment, hypoacusis, migraine, and myopathy, but also with hypertelorisms and acoustic nerve atrophy.

Arthrogryposis multiplex congenital, the occurrence of multiple joint contractures at birth, can in some cases be accompanied by insufficient myelination of peripheral nerves, muscular hypotonia, reduced tendon reflexes, and respiratory insufficiency. Recently mutations in the CASPR/CNTN1 complex have been associated with similar severe phenotypes and CNTNAP1 gene mutations, causing loss of the CASPR protein, were shown to cause severe, prenatal onset arthrogryposis multiplex congenita in four unrelated families. Here we report a consanguineous Arab family from Qatar with three children having an early lethal form of arthrogryposis multiplex congenita and a novel frameshift mutation in CNTNAP1. We further expand the existing CNTNAP1-associated phenotype to include profound cerebral and cerebellar atrophy.

Objectives.Although hereditary neuropathy with liability to pressure palsies (HNPP) presents with a distinct phenotype on history, clinical exam, and nerve conduction studies, it may be masked if diagnostic work-up suggests other causes.Case Report.In a 37-year-old male with pseudoradicular lumbar pain, neurological exam revealed sore neck muscles, peripheral facial nerve palsy, right anacusis and left hypoacusis, hemihypesthesia of the right face, mild distal quadriparesis, diffuse wasting, and generally reduced tendon reflexes. He had a history of skull fracture due to a gunshot behind the right ear and tuberculosis for which he had received adequate treatment for 3 years; MRI revealed a disc prolapse at C6/7 and Th11/12. Nerve conduction studies were indicative of demyelinating polyneuropathy with conduction blocks. Despite elevated antinuclear antibodies and elevated CSF-protein, HNPP was diagnosed genetically after having excluded vasculitis, CIDP, radiculopathy, and the side effects of antituberculous treatment.Conclusions.HNPP may manifest with mild, painless, distal quadriparesis. The diagnosis of HNPP may be blurred by a history of tuberculosis, tuberculostatic treatment, hepatitis, and the presence of elevated CSF-protein.

Friedreich ataxia (FRDA) is the most common inherited ataxia caused primarily by an intronic GAA.TTC triplet repeat expansion in the frataxin ( FXN ) gene. FXN RNA and protein levels are reduced in patients leading to progressive gait and limb ataxia, sensory loss, reduced tendon reflexes, dysarthria, absent lower limb reflexes, and loss of position and vibration sense. Neurological manifestations ensue from primary loss of dorsal root ganglia neurons and their associated axons ascending centrally in the spinal cord and peripherally in large myelinated nerves. Small noncoding RNAs such as microRNAs have been shown to be dysregulated in neurodegenerative diseases such as Alzheimer's and Huntington's disease. Here we report that hsa-miR-886-3p (miR-886-3p) was increased in patient cells as well as peripheral patient blood samples. Selective reduction in miR-886-3p by an anti-miR led to elevation of FXN message and protein levels without associated changes in histone marks at the FXN locus. Nevertheless, derepression of frataxin by a histone deacetylase inhibitor leads to a decrease in miR-886-3p. These results outline involvement of a small RNA, miR-886-3p in FRDA and a novel therapeutic approach to this disease using an anti-miR-886-3p.

Three patients with acute multiple cranial neuropathy following benign infectious disease are reported. Complete or partial ophthalmoplegia, as well as facial and bulbar dysfunction, were noted in all. Cranial nerve involvement was bilateral. Other neurological deficits included sensory loss in two patients and transiently reduced tendon reflexes in the left arm in one. One patient had positive serum anti-GQ1b immunoglobulin G antibody during the acute phase of the illness. The cerebrospinal fluid had a normal cell count in all three patients, with raised protein concentrations in two. Electrophysiological evaluation showed peripheral nerve dysfunction in two patients. All three patients improved either spontaneously or coincident with immunotherapy. Our patients had many clinical features resembling those of typical Guillain-Barre syndrome (GBS), and hence their disorder may represent a regional variant, that is, a cranial form, of GBS. This form of GBS accounted for 5% of the GBS patient population in our series.

We report an Austrian family with proximal muscle weakness and wasting predominantly of the shoulder girdle musculature, normal or slightly reduced distal muscle power, mild foot deformity, absent or reduced tendon reflexes in the lower limbs, and normal or slightly diminished sensation. Electrophysiologically, motor nerve conduction velocities were slowed to less than 33 m/s, distal latencies were prolonged, and compound motor action potentials were low. Sensory nerve conduction velocities were extremely reduced or no sensory potentials were recordable. Genetic testing in three affected individuals revealed a duplication of the chromosomal region 17p11.2. In addition, genetic testing for facioscapulohumeral muscular dystrophy (FSHD) revealed a 33 kb EcoRI fragment on chromosome 4q35 in one affected individual and in the clinically normal parent, whereas in a second affected person normal DNA-sizes were observed. These clinical findings define a new phenotypic variant associated with the Charcot-Marie-Tooth 1A duplication. This may be due to a mutation in another gene contained in the 1.5 Mb duplication although mutations in the peripheral myelin protein 22 gene have been excluded. Alternatively, the genetic background of other genes in the family may modify the phenotypic expression, as found in other inherited diseases. The unusual phenotype cannot be explained by the concomitant presence of FSHD despite some evidence for coexistance in one individual.

Hereditary neuropathy with liability to pressure palsy (HNPP; tomaculous neuropathy) is a rare autosomal dominant disorder caused by a loss of function of the peripheral myelin protein 22 gene ( PMP22 ; OMIM #601097) for which no curative treatment exists. Symptoms consist of recurrent painless episodes of focal sensory loss and muscle weakness, which are often provoked by nerve compression and resolve spontaneously within days to months.1 In this report, we describe the case of a female patient with HNPP who initially presented with symptoms of a painful neuropathy which were successfully treated with intravenous immunoglobulin G (IVIg), and the results of a double-blind, placebo-controlled n-of-one trial to assess the effectiveness of IVIg in this patient. In 2002, a 35-year-old female patient presented with a 15-month history of neuropathic pain in the right leg, and recurring episodes of weakness and sensory loss in the legs which resolved spontaneously after several weeks. Her medical and family history was unremarkable. Physical examination showed mild proximal weakness of the left leg (Medical Research Council (MRC) grade 4), severe weakness of the left foot extensors (MRC 0–2), hypoalgesia of the left hand and lower leg, and reduced tendon reflexes with absent Achilles reflexes. All additional investigations were normal, except electromyographic (EMG) studies which showed bilateral demyelinating conduction blocks at ulnar nerve compression sites, prolonged distal motor latencies of the ulnar, tibial, peroneal and median nerves, and absent F-waves in peroneal and right tibial nerves, …

Cold-induced sweating syndrome type 1 (CISS1) is a rare disorder characterized by profuse sweating in a cold environment, determined by mutations in cytokine receptor–like factor 1 ( CRLF1 ).1 Its pathogenesis is not fully understood. It has been demonstrated in vitro that CRLF1 may be involved in inducing differentiation from a noradrenergic to a cholinergic transmitter phenotype. During development, catecholaminergic and cholinergic neurotransmission is required for the induction of secretory function, whereas cholinergic transmission becomes crucial for the maintenance of the secretory responsiveness.2 The abnormal sweat response in CISS1 could be also related to alterations in temperature signals acting on hypothalamus and preoptic areas.1 We report clinical, molecular, skin biopsy, and temperature monitoring data of an Italian boy with CISS1. ### Case report. A 16-year-old boy had come to our observation at 1 year of age. His parents were healthy and unrelated. A brother, with facial dysmorphisms and hypotonia, had died at age 3 months from bronchopulmonary infection. Our patient was hypotonic at birth and experienced severe feeding difficulties. He had elongated face, high-arched palate, weak cry, large pinnae, short hands, tapering fingers, clinodactyly, and reduced tendon reflexes. Concentric needle EMG, nerve conduction velocity (NCV) studies (ulnar, median, peroneal, tibial, and sural nerves), and repetitive nerve stimulation testing excluded a …

Charcot–Marie–Tooth disease (CMT) is an heterogeneous group of hereditary neuropathies characterized by weakness and atrophy of the limbs, loss of sensation and absent or reduced tendon reflexes. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) causes progressive or recurrent weakness and numbness of the limbs. Both CMT and CIDP share similar nerve conduction study abnormalities (reduced amplitude of sensory and motor potentials, and reduced conduction velocity). The aim of our study was to compare the ultrasound (US) data recorded in genetic neuropathy (CMT) and inflammatory neuropathy (CIDP). We enrolled 10 patients with CMT type 1A and 10 patients with CIDP. In this study we compared left and right median nerve cross-sectional area (CSA) and echogenicity nerve in the forearm, between two groups of patients to evaluate a possible difference. Three US classes were identified based on CSA and echogenicity. For all patient included neurophysiological assessment was used to estimate a possible correlation between the nerve conduction study variables and US data. US of the nerve can be a tool of significant value in the differential diagnosis in different neuropathies.

Objectives Few data are available about myopathy and polyneuropathy as rare side effects of chloroquine treatment. Even more rarely are cerebrospinal fluid (CSF) abnormalities in chloroquine polyneuropathy/myopathy. Case description The patient is an 81-year-old woman with a 30-year history of chronic polyarthritis. As a basic therapy, she received chloroquine (250 mg per day) since 1997. Already, 1 year later she developed slowly progressive gait disturbance, which led to recurrent falls, and forced her to use crutches and other orthotic devices. Since March 2001, she was no longer able to climb stairs. Since then she also developed sensory disturbances in both lower limbs. Clinical neurological investigation revealed weakness and wasting of all four limbs and reduced tendon reflexes and stocking-type sensory disturbances. Nerve conduction studies were indicative of an axonal polyneuropathy. Electromyography was non-specifically abnormal. Muscle biopsy of the gastrocnemius muscle disclosed neuropathic and myopathic features and frequent fibers with partially rimmed vacuoles, containing concentrically or parallelly sliced inclusions. CSF investigations disclosed increased protein but otherwise normal findings. Five months after discontinuation of chloroquine and replacement by leflunomid, there was marked clinical improvement. Conclusions Chloroquine polyneuropathy/myopathy may go along with increased CSF protein. Discontinuation of the causative agent results in prompt recovery of the described abnormalities.

not utilizable. Biopsy of the right gastrocnemius muscle revealed a chronic neurogenic pattern. Since the age of 22 years she noted impaired hearing on the right side. At the age of 26 years, hypothyroidism was diagnosed and levothyroxin prescribed. At the age of 27 years she started to take phentermine to reduce her overweight. Eight weeks later she additionally received nandrolone to compensate for progressive wasting. Three weeks later she stopped phentermine and nandrolone at 100 mg/ week after she had developed blurred vision of the right eye. Ophthalmologic investigation revealed right-sided reduced vision and a papilledema. Clinical neurologic examination revealed distal weakness in all four limbs, with lower limb predominance, and reduced respectively absent deep tendon reflexes. Blood work and CSF investigations were non-informative. Nerve conduction velocities were 18– 22 m/s. Visually-evoked-potentials initially revealed an absent response upon stimulation of the right eye and later on prolongation of the P100 latencies bilaterally. Cerebral MRI was normal. Under corticosteroids, papilledema continuously resolved over weeks. Molecular genetic analysis revealed a common tandem duplication in the PMP22 gene at 17p11.2. HMSN1A was also diagnosed in her father, who had developed sensorimotor deficits and foot deformity without other features as in his daughter since the age of Dear Sir, The autosomal-dominantly inherited 1.5-Mb tandem duplication in the PMP22 gene at 17p11.2 usually manifests as hereditary sensorimotor polyneuropathy with foot deformity (HMSNIA) [1, 2] . In single cases, however, it has been found in association with additional features, such as sensorineural hearing loss, moderate developmental delay, gait disturbance, autism-related disorder, mild dysmorphic features, or growth factor deficiency [3] . The coexistence of sensorimotor polyneuropathy with tremor, ataxia, sensorineural hearing loss, hypothyroidism, short stature, and papilledema has not been reported. The patient is a 27-year-old HIV-negative woman, height 163 cm, weight 73 kg, who had peculiarly walked tiptoe since childhood and had pes cavus. Since the age of 17 years she additionally developed slowly progressive gait disturbance, easy fatigability, and numbness of the distal upper and lower limbs. She had to walk with all her concentration not to stumble. Motor deficits in the lower limbs resulted in inability to climb stairs, difficulties when walking or running, and to get up from the floor without assistance. Diagnostic workup at the age of 20 years revealed distal weakness of all four extremities with rightsided and lower limb predominance, reduced tendon reflexes, muscular hypotonia, and endpoint ataxia. Blood work was normal. Biopsy of the right sural nerve was Received: October 13, 2006 Accepted: October 14, 2006 Published online: December 18, 2006