Chronic Sensorimotor Polyneuropathy Research Articles

Clinical and neurophysiological findings in patients with hereditary neuropathy with liability to pressure palsy and chromosome 17p11.2 deletion

IntroductionHereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder, typically presenting with recurrent episodes of mononeuropathy in nerves susceptible to compression, with similar neurophysiological characteristics. However, other clinical and neurophysiological presentations have been reported. MethodsWe retrospectively analysed the clinical and neurophysiological characteristics of 20 patients with genetically confirmed HNPP. Sixteen patients were studied in our department between 1996 and 2016. ResultsIn addition to the typical characteristics of HNPP, we found atypical forms including recurrent positional sensory symptoms in 3 patients, chronic sensorimotor polyneuropathy in one, and non-progressive mononeuropathy in one. Onset was early in 2 patients: one at the age of 7 years, with common peroneal nerve injury, and another at birth, with brachial plexus involvement. By frequency, the main pathological findings in the nerve conduction study were: decreased sensory nerve conduction velocity in the sural (84%) and the median and superficial peroneal nerves (94%); decreased motor nerve conduction velocity in the ulnar nerve through the elbow (97%), and increased motor distal latency of the median and deep peroneal nerves (74%). ConclusionOur results confirm the clinical variability of HNPP, with the most frequent nerve conduction study findings being the generalised decrease in sensory nerve conduction velocity, in addition to motor involvement, mainly in locations susceptible to nerve compression. The nerve conduction study can detect typical, atypical, and asymptomatic cases of HNPP.

Diabetic Polyneuropathy

Diabetes mellitus is a chronic disease that develops against the background of insulin deficiency as a result of a decrease in its production or impaired receptor perception by target cells. As a result of impaired glucose metabolism, a state of chronic hyperglycemia develops, which has a detrimental effect on a number of organs and systems. One of such systems that are negatively affected by an increase in glucose concentration against the background of a general violation of all types of metabolism is the nervous system, in particular, its peripheral part. Approximately every second patient with diabetes eventually develops a state of diabetic polyneuropathy (chronic sensorimotor polyneuropathy or distal symmetric polyneuropathy), which is characterized by progressive degeneration of peripheral nerves with the development of pain, motor disorders and loss of sensitivity.

Hallazgos clínico-neurofisiológicos en neuropatías hereditarias sensibles a la presión con deleción del cromosoma 17p11.2

IntroductionHereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder, typically presenting with recurrent episodes of mononeuropathy in nerves susceptible to compression, with similar neurophysiological characteristics. However, other clinical and neurophysiological presentations have been reported. MethodsWe retrospectively analysed the clinical and neurophysiological characteristics of 20 patients with genetically confirmed HNPP. Sixteen patients were studied in our department between 1996 and 2016. ResultsIn addition to the typical characteristics of HNPP, we found atypical forms including recurrent positional sensory symptoms in 3 patients, chronic sensorimotor polyneuropathy in one, and non-progressive mononeuropathy in one. Onset was early in 2 patients: one at the age of 7 years, with common peroneal nerve injury, and another at birth, with brachial plexus involvement. By frequency, the main pathological findings in the nerve conduction study were: decreased sensory nerve conduction velocity in the sural (84%) and the median and superficial peroneal nerves (94%); decreased motor nerve conduction velocity in the ulnar nerve through the elbow (97%), and increased motor distal latency of the median and deep peroneal nerves (74%). ConclusionOur results confirm the clinical variability of HNPP, with the most frequent nerve conduction study findings being the generalised decrease in sensory nerve conduction velocity, in addition to motor involvement, mainly in locations susceptible to nerve compression. The nerve conduction study can detect typical, atypical, and asymptomatic cases of HNPP.

Clinical and neurophysiological features of the hereditary neuropathy with liability to pressure palsy due to the 17p11.2 deletion.

The hereditary neuropathy with liability to pressure palsies (HNPP) is an autossomal dominant disorder manifesting recurrent mononeuropathies. Objective Evaluate its clinical and nerve conduction studies (NCS) characteristics, searching for diagnostic particularities. Method We reviewed the neurological manifestations of 39 and the NCS of 33 patients. Results Family history was absent in 16/39 (41%). The onset complaints were weakness in 24, pain in 6, sensory deficit in 5 and paresthesias in 4. Pain was seen in 3 other patients. The following neuropathy patterns were found: multiple mononeuropathy (26), mononeuropathy (7), chronic sensorimotor polyneuropathy (4), chronic sensory polyneuropathy (1) and unilateral brachial plexopathy (1). NCS showed a sensorimotor neuropathy with focal conduction slowing in 31, two had mononeuropathy and another brachial plexopathy. Conclusion HNPP presentation is variable and may include pain. The most frequent pattern is of an asymmetrical sensory and motor neuropathy with focal slowing at specific topographies on NCS.

Multiple endocrine neoplasia type 1 presenting as refractory epilepsy and polyneuropathy — A case report

Hypoglycemia is a well recognized cause of acute symptomatic seizures. The fact that hypoglycemia can cause peripheral neuropathy is less appreciated. We describe a case of insulinoma associated peripheral neuropathy. A 17 year-old previously healthy man was referred for investigation of refractory epilepsy. A history of recurrent seizures, slowly progressive weakness of his feet and hands, and weight gain was obtained. Physical examination showed signs of a chronic sensory–motor polyneuropathy. He was diagnosed with insulinoma and primary hyperparathyroidism, characterizing multiple endocrine neoplasia, type 1 syndrome. Cases of insulinoma associated peripheral neuropathy are very rare. The more characteristic clinical picture appears to be distal weakness, worse in the intrinsic hand and feet muscles, and no or mild sensory signs. Peripheral nervous system symptoms may not completely resolve, despite removal of the cause of hyperinsulinism/hypoglycemia and full reversion of central nervous system symptoms. Mechanisms underlying hypoglycemic neuropathy are still poorly understood.

Update on the management of diabetic polyneuropathies.

The prevalence of diabetic polyneuropathy (DPN) can approach 50% in subjects with longer-duration diabetes. The most common neuropathies are generalized symmetrical chronic sensorimotor polyneuropathy and autonomic neuropathy. It is important to recognize that 50% of subjects with DPN may have no symptoms and only careful clinical examination may reveal the diagnosis. DPN, especially painful diabetic peripheral neuropathy, is associated with poor quality of life. Although there is a better understanding of the pathophysiology of DPN and the mechanisms of pain, treatment remains challenging and is limited by variable efficacy and side effects of therapies. Intensification of glycemic control remains the cornerstone for the prevention or delay of DPN but optimization of other traditional cardiovascular risk factors may also be of benefit. The management of DPN relies on its early recognition and needs to be individually based on comorbidities and tolerability to medications. To date, most pharmacological strategies focus upon symptom control. In the management of pain, tricyclic antidepressants, selective serotonin noradrenaline reuptake inhibitors, and anticonvulsants alone or in combination are current first-line therapies followed by use of opiates. Topical agents may offer symptomatic relief in some patients. Disease-modifying agents are still in development and to date, antioxidant α-lipoic acid has shown the most promising effect. Further development and testing of therapies based upon improved understanding of the complex pathophysiology of this common and disabling complication is urgently required.

Chronic Sensorimotor Polyneuropathy Associated With Tacrolimus Immunosuppression in Renal Transplant Patients: Case Reports

Tacrolimus is used widely for immunosuppression following transplantation. It has rarely been linked to the development of peripheral neuropathy. However, one study also reported improvement in peripheral neuropathy after tacrolimus use. We have reported herein two patients who developed chronic sensorimotor polyneuropathy after tacrolimus use following renal transplantation. One patient had an unusual presentation with bilateral facial and extremity weakness and a relapsing course. The other patient presented with focal sensory symptoms in one hand. Electrophysiological studies confirmed widespread, predominantly demyelinating or axonal polyneuropathy. We concluded that patients on tacrolimus should be carefully monitored for symptoms suggestive of peripheral neuropathy.

Medial dorsal superficial peroneal nerve studies in patients with polyneuropathy and normal sural responses

We studied medial dorsal superficial peroneal (MDSP) nerves in 52 patients with clinical evidence of mild chronic sensorimotor polyneuropathy and normal sural nerve responses, in order to assess the diagnostic sensitivity and usefulness of MDSP nerve testing in electrodiagnostic practice. To determine the effect of age on MDSP nerve parameters, 98 normal subjects were also examined. Electrodiagnostic evaluation involved studies of motor nerve conduction in tibial, peroneal, and median nerves; sensory nerve conduction in sural, MDSP, median, and radial nerves; tibial and peroneal nerve F waves; H reflexes from the soleus muscles; and needle electromyography of gastrocnemius and abductor hallucis muscles. Among the patients, 49% had low-amplitude sensory responses in MDSP nerves and 57% had either slowing of sensory conduction velocity or no sensory responses on proximal stimulation. MDSP nerve amplitude, tibial nerve motor velocity, and H reflexes were the most sensitive for detection of mild chronic symmetrical axonal sensorimotor polyneuropathy. MDSP nerve testing should be included in the routine electrodiagnostic evaluation of patients with suspected polyneuropathy and normal sural nerve responses.

Valeur diagnostique du profil neurophysiologique classique dans les différents phénotypes de la neuropathie héréditaire sensible à la pression

Purpose. – We looked for electrodiagnostic features that raise suspicion of hereditary neuropathy with liability to pressure palsies (HNPP). Method. – A retrospective review of eight cases with confirmed histologic (one case) or chromosome 17 deletion (seven cases) analysis was performed. Results. – Autosomal dominant disease was present in 63% of the patients, 75% being men. Mean age at examination and at first symptom was 27 and 22 years respectively. Five patients have one or more acute nerve palsies, without residual deficit, but one presented sensory symptoms in internal saphena territory. Three patients had others phenotypes: a man presented with four episodes of facial palsy and one woman was asymptomatic; another patient with diabetes mellitus presented an associated chronic sensorimotor polyneuropathy. In agreement with other studies of HNPP we found in most patients a diffuse increase in distal motor latence, contrasting with normal or moderately decreased motor nerve conduction velocity, multiple electrophysiologic entrapment and diffuse reduction in sensory nerve action potential and/or velocity. However, this electrophysiological pattern was incomplete or masked in HNPP with cranial nerves palsies, in asymptomatic form of HNPP or in HNPP associated with polyneuropathy. Conclusion. – These data confirm the clinical phenotypic heterogeneity of the 17p11.2 deletion and highlight the limits of the classic electrophysiological pattern in asymptomatic HNPP or associated with uncommon clinical features.

Prospective follow-up study of chronic polyneuropathy of undetermined cause.

Forty consecutive patients with chronic sensorimotor polyneuropathy of undetermined cause were followed to determine disease progression and prognosis. They had had neurological symptoms for at least 1 year before presentation. Neurophysiological examination in all patients showed chronic axonal degeneration, which was confirmed by sural nerve biopsy. Patients were reviewed every 3 months. Laboratory tests were performed every 6 months for the first 2 years and then annually. Neurophysiological examination was performed annually in all patients. Patients were followed up for at least 4 years. In no instance was a possible etiological factor detected during follow-up. The clinical and electrophysiological findings had a slowly progressive course. We suggest that patients with a chronic polyneuropathy of undetermined cause despite detailed investigations do not require further extensive and expensive laboratory tests and neurophysiological studies during follow-up.

Complement-Mediated Demyelination in Patients with IgM Monoclonal Gammopathy and Polyneuropathy

We investigated the role of complement in the pathogenesis of the demyelinating polyneuropathy that occurs in some patients with IgM monoclonal gammopathy. Seven patients with chronic sensorimotor polyneuropathy and IgM monoclonal gammopathy were examined. In six patients, the monoclonal protein recognized an epitope shared by myelin-associated glycoprotein and two peripheral-nerve glycolipids, whereas in one patient, IgM bound to an unidentified myelin antigen. Direct and indirect immunofluorescence and immunoperoxidase assays showed colocalization along the myelin sheaths of peripheral-nerve fibers of monoclonal protein with complement components C1q, C3d, and C5. In addition, terminal-complement complex that was not associated with S protein was detected in myelin sheaths. It appeared that alterations in myelin geometry caused by the separation of myelin lamellae corresponded to sites at which terminal-complement complex was deposited. We conclude that demyelination in polyneuropathy associated with IgM monoclonal gammopathy may be mediated by complement.

Peripheral neuropathy associated with monoclonal gammopathy. Studies of intraneural injections of monoclonal immunoglobulin sera.

A causal relationship between paraproteinemia and neuropathies has been suggested. We studied three patients with chronic sensorimotor polyneuropathy associated with plasma cell dyscrasia and monoclonal gammopathies (IgGK, IgMK, IgA lambda). Sural nerve biopsies showed mild (2 cases) to moderate loss of myelinated fibers (1 case). Teased single fiber studies showed segmental demyelination-remyelination in two patients. Direct immunofluorescence demonstrated immune deposits of the myelin sheath of the same specificity as the serum paraprotein, IgGK (1 of 3 cases). Treatment with prednisone, melphalan or chlorambucil, and plasmapheresis resulted in remission (1 case), partial improvement (1 case), or had no effect (1 case), although reduction of monoclonal immunoglobulin occurred in all. To investigate the role the paraproteins might play in the pathogenesis of the neuropathy, patients' serum was injected intraneurally into rat sciatic nerves. None of the animals developed weakness, slowing of in vitro conduction of sciatic nerve, or significant evidence of demyelination by light- or electron-microscopy or teased single fiber studies 48 hours postinjection. Similar injections of rabbit serum with experimental allergic neuritis (EAN) produced focal segmental demyelination. Our studies employing an in vivo bioassay technique failed to establish antimyelin activity of monoclonal immunoglobulin sera.

Evoked electrospinogram in spinal cord and peripheral nerve disorders.

Spinal cord evoked potentials have been studied by means of intrathecal application in 80 patients with various spinal cord and peripheral nerve disorders. The segmental spinal cord potentials are normal in acute motor polyneuropathy, generalized anterior horn cell disease and in discrete lesions of dorso-lumbar segments. On the other hand, the first component of the segmental response is delayed, reduced and sometimes dispersed or lost in chronic sensory-motor polyneuropathy and in hereditary spinocerebellar degeneration. the reduction in amplitude is also present in multiple sclerosis with clinical signs of dorsal funiculus involvement. In compressive lesions of the cauda-conus, recordings of lower thoracic intervertebral level show that the segmental responses are delayed with marked amplitude reduction. The potentials recorded from lumbo-sacral segments show a greater the amplitude of the second component proportionally to the first one as the duration of second component is longer in spastic paraplegia regardless of its etiology. The cervical tractus response is seen to be markedly slowed with a reduction of amplitude or is often absent in chronic polyneuropathy, spinocerebellar degeneration and in multiple sclerosis. The primary sensory neurones lying both in periphery and in the dorsal column are assumed to be responsible for the segmental evoked potentials especially for the first component. the late slow component is related to the activation of interneurones situated within the segmental gray matter and segmental collaterals of the dorsal root fibres carrying impulses to those cells. Cervical tractus responses are mostly formed by the dorsal column fibres and their physiological action upon demyelination is similar to that of the peripheral nerves.