Jeffrey W. Ralph

Visualizing axon regeneration after peripheral nerve injury with magnetic resonance tractography

Diffusion tensor imaging (DTI) with tractography is an MRI technique that can visualize nerve pathways by taking advantage of anisotropy of water diffusion in tracts with longitudinally oriented fibers. To date, no study in humans has shown that DTI and tractography can follow regeneration of axons during recovery from traumatic peripheral nerve injury. We show that tractography is able to identify regenerating axons advancing through a graft repair of an injured nerve, and demonstrate correlation with evidence of recovery on serial clinical, electrodiagnostic, and muscle MRI assessments.

Quantitative ultrasound of denervated hand muscles

Presentations to the neuromuscular clinic commonly involve hand muscle denervation, but few studies have evaluated hand muscle ultrasound.

Transient hyperckemia in the setting of neuromyelitis optica (NMO).

Neuromyelitis optica (NMO) is characterized by inflammatory demyelinating lesions of the spinal cord and optic nerves from an autoimmune response against water channel aquaporin‐4 (AQP4). We report 2 patients with transient hyperCKemia associated with NMO suggesting possible skeletal muscle damage. Methods: Patient 1 was a 72‐year‐old man who presented with muscle soreness and elevated serum creatine kinase (CK) preceding an initial attack of NMO. Patient 2 was a 25‐year‐old woman with an established diagnosis of NMO who presented with diffuse myalgias, proximal upper extremity weakness, and hyperCKemia. Muscle biopsies were obtained for histopathologic evaluation, protein gel electrophoresis, immunofluorescence, and complement staining. Results: In both patients the muscle showed only mild variation in fiber diameter. There were no inflammatory changes or muscle fiber necrosis, though there was reduced AQP4 expression and deposition of activated complement. Conclusions: Complement‐mediated sarcolemmal injury may lead to hyperCKemia in NMO. Muscle Nerve 50: 859–862, 2014

Incomplete Brown-Séquard syndrome after methamphetamine injection into the neck

Brown-Sequard syndrome classically results from spinal cord hemisection, most commonly due to trauma and occasionally from tumor or infarction.1 Clinically, it manifests as complete loss of ipsilateral light touch sensation and proprioception, loss of contralateral pain and temperature sensation, and ipsilateral motor paralysis. Most patients, however, experience an incomplete Brown-Sequard syndrome with only partial sensory and motor impairment.2 We describe a previously undocumented cause of incomplete Brown-Sequard syndrome: direct injection of methamphetamine into the neck. A 25-year-old male injection-drug user developed acute-onset right-sided paralysis and burning dysesthesias after a friend inserted a 2- to 3-cm needle immediately superior to the right clavicle near the sternoclavicular joint, advanced parallel to the clavicle, and injected a methamphetamine bolus into the neck. Immediately after injection, the patient experienced a brief burning sensation in his tongue and confusion without loss of consciousness. After 30 minutes, he noticed tightening of his right facial muscles, progressive right arm and leg weakness, and right-sided dysesthesia. He …

Adult-Onset Fatal Neurohepatopathy in a Woman Caused by MPV17 Mutation

Hepatocerebral mitochondrial DNA depletion syndromes are classically considered diseases of early childhood, typically affecting the liver, peripheral, and central nervous systems with a rapidly progressive course. Evidence is emerging that initial symptom onset can extend into adulthood, though few such cases have been reported. We describe a 25-year-old woman who presented initially with secondary amenorrhea, followed by a megaloblastic anemia, lactic acidosis, leukoencephalopathy, progressive peripheral neuropathy, and liver cirrhosis. An apparently homozygous P98L mutation was identified in MPV17, a gene associated with a lethal infantile neurohepatopathy. Homozygosity for the same allele was recently reported in a man with a similar hepatic and neurologic phenotype. This is the first clinical report of an adult female with this disorder, and the first to describe amenorrhea and megaloblastic anemia as likely associated symptoms.

Sonographic diagnosis of true neurogenic thoracic outlet syndrome

A 32-year-old woman presented with a 5-year history of left shoulder pain, medial hand and forearm numbness, and progressive hand weakness and atrophy. Electrodiagnostic studies were characteristic of true neurogenic thoracic outlet syndrome,1 and a chest X-ray showed bilateral elongated C7 transverse processes. High-resolution ultrasound studies revealed compression of the left lower trunk (LT) between a fibrous band and artery (figure, A). Magnetic resonance neurography (figure, B) and operative exploration (figure, C) confirmed the ultrasound findings. Clinical improvement was noted following surgical neurolysis of the LT. High-resolution ultrasound may be a useful and quick bedside tool to identify causative structural pathology in this classic neuromuscular disorder.

Dual reinnervation of biceps muscle after side-to-side anastomosis of an intact median nerve and a damaged musculocutaneous nerve

Traumatic peripheral nerve injury can lead to significant long-term disability for previously healthy persons. Damaged nerve trunks have been traditionally repaired using cable grafts, but nerve transfer or neurotization procedures have become increasingly popular because the axonal regrowth distances are much shorter. These techniques sacrifice the existing nerve pathway, so muscle reinnervation depends entirely on the success of the repair. Providing a supplemental source of axons from an adjacent intact nerve by using side-to-side anastomosis might reinnervate the target muscle without compromising the function of the donor nerve. The authors report a case of biceps muscle reinnervation after side-to-side anastomosis of an intact median nerve to a damaged musculocutaneous nerve. The patient was a 34-year-old man who had sustained traumatic injury primarily to the right upper and middle trunks of the brachial plexus. At 9 months after the injury, because of persistent weakness, the severely damaged upper trunk of the brachial plexus was repaired with an end-to-end graft. When 8 months later biceps function had not recovered, the patient underwent side-to-side anastomosis of the intact median nerve to the adjacent distal musculocutaneous nerve via epineural windows. By 9 months after the second surgery, biceps muscle function had returned clinically and electrodiagnostically. Postoperative electromyographic and nerve conduction studies confirmed that the biceps muscle was being reinnervated partly by donor axons from the healthy median nerve and partly by the recovering musculocutaneous nerve. This case demonstrates that side-to-side anastomosis of an intact median to an injured musculocutaneous nerve can provide dual reinnervation of the biceps muscle while minimizing injury to both donor and recipient nerves.

Retrospective natural history of thymidine kinase 2 deficiency

Background Thymine kinase 2 (TK2) is a mitochondrial matrix protein encoded in nuclear DNA and phosphorylates the pyrimidine nucleosides: thymidine and deoxycytidine. Autosomal recessive TK2 mutations cause a spectrum of disease from infantile onset to adult onset manifesting primarily as myopathy. Objective To perform a retrospective natural history study of a large cohort of patients with TK2 deficiency. Methods The study was conducted by 42 investigators across 31 academic medical centres. Results We identified 92 patients with genetically confirmed diagnoses of TK2 deficiency: 67 from literature review and 25 unreported cases. Based on clinical and molecular genetics findings, we recognised three phenotypes with divergent survival: (1) infantile-onset myopathy (42.4%) with severe mitochondrial DNA (mtDNA) depletion, frequent neurological involvement and rapid progression to early mortality (median post-onset survival (POS) 1.00, CI 0.58 to 2.33 years); (2) childhood-onset myopathy (40.2%) with mtDNA depletion, moderate-to-severe progression of generalised weakness and median POS at least 13 years; and (3) late-onset myopathy (17.4%) with mild limb weakness at onset and slow progression to respiratory insufficiency with median POS of 23 years. Ophthalmoparesis and facial weakness are frequent in adults. Muscle biopsies show multiple mtDNA deletions often with mtDNA depletion. Conclusions In TK2 deficiency, age at onset, rate of weakness progression and POS are important variables that define three clinical subtypes. Nervous system involvement often complicates the clinical course of the infantile-onset form while extraocular muscle and facial involvement are characteristic of the late-onset form. Our observations provide essential information for planning future clinical trials in this disorder.

Pearls & Oy-sters: The use of CT venography in Hirayama disease

An 18-year-old, left-handed North Indian man presented with a 2-year history of wasting and weakness …

Cervical Myelopathy Caused by Injections into the Neck.

Three cases of longitudinally extensive cervical myelopathies temporally associated with neck injections are presented. The spinal cord injury was similar radiographically, despite a number of different needle approaches and substances injected. In recent years, there have been reports of an acute cervical myelopathy immediately following an injection procedure in the neck. Various explanations have been offered for this unfortunate complication, including (1) direct injection into the cord leading to traumatic injury, (2) injection of particulate matter into the arterial supply of the cord causing microvascular embolism and spinal cord infarction, and (3) intraneural injection of the chemical with centripetal spread of the injectant from the nerve trunk to the substance of the cord. The merits of each of these 3 mechanisms in explaining these cases are discussed. Albeit rare, acute cervical myelopathy should be considered a potential complication from any deep injection of chemicals into the neck.