Combined therapy of telbivudine and pegylated interferon α-2a induced sensory neuropathy:2 case reports

Objective To report the clinical and pathological features of the sensory neuropathy caused by a combined therapy of telbivudine and pegylated interferon α-2a in 2 patients with hepatitis B virus infection Methods Two male patients aged 48(case 1)and 20(case 2),who suffered from hepatitis B virus infection.were given telbivudine and pegylated interferon α-2a.After 4 months treatment,both patients developed numbness and pain in the lower limbs.The physical examination showed decreased pain sensation in distal extremities.Hypahidrosis appeared in distal extremities.The nails were pale changed in fingers and toes in cage 1.Case 2 presented mild weakness in the proximal muscle of lower limbs and the tendon reflex was decreased in both lower limbs.His 8erunl creatine kinase level was mild elevated.The electromyography examination and sural nerve biopsies were performed on both patients.Results Electromyography examination showed significant decrease of amplitude of sensory nerve action potentials and mild decrease of sensory nerve conduction velocities in both patients.The amplitude of motor nerve action potentials was also decreased in case 2.Light microscope examination revealed middle reduction of myelinated fibers,wallerian degeneration of myelinated fibers and small clusbers of regenerated fibers in sural nerve.Electro microscopy examination revealed the loss of unmyehnated nerve fibers.After the combined therapy was stopped and vitamin B,CoQ10 and L-camitine were administered,the patients recovered gradually.Conclusions Combined therapy of telbivudine and pegylated interferon α-2a may cause sensory neuropathy with electrophsiological and pathological abnormalities of axonal lesions.The sensory neuropathy induced by the combined therapy may be reversible.     

Combined therapy of telbivudine and pegylated interferon α-2a induced sensory neuropathy:2 case reports

Objective To report the clinical and pathological features of the sensory neuropathy caused by a combined therapy of telbivudine and pegylated interferon α-2a in 2 patients with hepatitis B virus infection Methods Two male patients aged 48(case 1)and 20(case 2),who suffered from hepatitis B virus infection.were given telbivudine and pegylated interferon α-2a.After 4 months treatment,both patients developed numbness and pain in the lower limbs.The physical examination showed decreased pain sensation in distal extremities.Hypahidrosis appeared in distal extremities.The nails were pale changed in fingers and toes in cage 1.Case 2 presented mild weakness in the proximal muscle of lower limbs and the tendon reflex was decreased in both lower limbs.His 8erunl creatine kinase level was mild elevated.The electromyography examination and sural nerve biopsies were performed on both patients.Results Electromyography examination showed significant decrease of amplitude of sensory nerve action potentials and mild decrease of sensory nerve conduction velocities in both patients.The amplitude of motor nerve action potentials was also decreased in case 2.Light microscope examination revealed middle reduction of myelinated fibers,wallerian degeneration of myelinated fibers and small clusbers of regenerated fibers in sural nerve.Electro microscopy examination revealed the loss of unmyehnated nerve fibers.After the combined therapy was stopped and vitamin B,CoQ10 and L-camitine were administered,the patients recovered gradually.Conclusions Combined therapy of telbivudine and pegylated interferon α-2a may cause sensory neuropathy with electrophsiological and pathological abnormalities of axonal lesions.The sensory neuropathy induced by the combined therapy may be reversible.     

Combined therapy of telbivudine and pegylated interferon α-2a induced sensory neuropathy:2 case reports

Objective To report the clinical and pathological features of the sensory neuropathy caused by a combined therapy of telbivudine and pegylated interferon α-2a in 2 patients with hepatitis B virus infection Methods Two male patients aged 48(case 1)and 20(case 2),who suffered from hepatitis B virus infection.were given telbivudine and pegylated interferon α-2a.After 4 months treatment,both patients developed numbness and pain in the lower limbs.The physical examination showed decreased pain sensation in distal extremities.Hypahidrosis appeared in distal extremities.The nails were pale changed in fingers and toes in cage 1.Case 2 presented mild weakness in the proximal muscle of lower limbs and the tendon reflex was decreased in both lower limbs.His 8erunl creatine kinase level was mild elevated.The electromyography examination and sural nerve biopsies were performed on both patients.Results Electromyography examination showed significant decrease of amplitude of sensory nerve action potentials and mild decrease of sensory nerve conduction velocities in both patients.The amplitude of motor nerve action potentials was also decreased in case 2.Light microscope examination revealed middle reduction of myelinated fibers,wallerian degeneration of myelinated fibers and small clusbers of regenerated fibers in sural nerve.Electro microscopy examination revealed the loss of unmyehnated nerve fibers.After the combined therapy was stopped and vitamin B,CoQ10 and L-camitine were administered,the patients recovered gradually.Conclusions Combined therapy of telbivudine and pegylated interferon α-2a may cause sensory neuropathy with electrophsiological and pathological abnormalities of axonal lesions.The sensory neuropathy induced by the combined therapy may be reversible.     

Combined therapy of telbivudine and pegylated interferon α-2a induced sensory neuropathy:2 case reports

Objective To report the clinical and pathological features of the sensory neuropathy caused by a combined therapy of telbivudine and pegylated interferon α-2a in 2 patients with hepatitis B virus infection Methods Two male patients aged 48(case 1)and 20(case 2),who suffered from hepatitis B virus infection.were given telbivudine and pegylated interferon α-2a.After 4 months treatment,both patients developed numbness and pain in the lower limbs.The physical examination showed decreased pain sensation in distal extremities.Hypahidrosis appeared in distal extremities.The nails were pale changed in fingers and toes in cage 1.Case 2 presented mild weakness in the proximal muscle of lower limbs and the tendon reflex was decreased in both lower limbs.His 8erunl creatine kinase level was mild elevated.The electromyography examination and sural nerve biopsies were performed on both patients.Results Electromyography examination showed significant decrease of amplitude of sensory nerve action potentials and mild decrease of sensory nerve conduction velocities in both patients.The amplitude of motor nerve action potentials was also decreased in case 2.Light microscope examination revealed middle reduction of myelinated fibers,wallerian degeneration of myelinated fibers and small clusbers of regenerated fibers in sural nerve.Electro microscopy examination revealed the loss of unmyehnated nerve fibers.After the combined therapy was stopped and vitamin B,CoQ10 and L-camitine were administered,the patients recovered gradually.Conclusions Combined therapy of telbivudine and pegylated interferon α-2a may cause sensory neuropathy with electrophsiological and pathological abnormalities of axonal lesions.The sensory neuropathy induced by the combined therapy may be reversible.     

Combined therapy of telbivudine and pegylated interferon α-2a induced sensory neuropathy:2 case reports

Objective To report the clinical and pathological features of the sensory neuropathy caused by a combined therapy of telbivudine and pegylated interferon α-2a in 2 patients with hepatitis B virus infection Methods Two male patients aged 48(case 1)and 20(case 2),who suffered from hepatitis B virus infection.were given telbivudine and pegylated interferon α-2a.After 4 months treatment,both patients developed numbness and pain in the lower limbs.The physical examination showed decreased pain sensation in distal extremities.Hypahidrosis appeared in distal extremities.The nails were pale changed in fingers and toes in cage 1.Case 2 presented mild weakness in the proximal muscle of lower limbs and the tendon reflex was decreased in both lower limbs.His 8erunl creatine kinase level was mild elevated.The electromyography examination and sural nerve biopsies were performed on both patients.Results Electromyography examination showed significant decrease of amplitude of sensory nerve action potentials and mild decrease of sensory nerve conduction velocities in both patients.The amplitude of motor nerve action potentials was also decreased in case 2.Light microscope examination revealed middle reduction of myelinated fibers,wallerian degeneration of myelinated fibers and small clusbers of regenerated fibers in sural nerve.Electro microscopy examination revealed the loss of unmyehnated nerve fibers.After the combined therapy was stopped and vitamin B,CoQ10 and L-camitine were administered,the patients recovered gradually.Conclusions Combined therapy of telbivudine and pegylated interferon α-2a may cause sensory neuropathy with electrophsiological and pathological abnormalities of axonal lesions.The sensory neuropathy induced by the combined therapy may be reversible.     

Combined therapy of telbivudine and pegylated interferon α-2a induced sensory neuropathy:2 case reports

Objective To report the clinical and pathological features of the sensory neuropathy caused by a combined therapy of telbivudine and pegylated interferon α-2a in 2 patients with hepatitis B virus infection Methods Two male patients aged 48(case 1)and 20(case 2),who suffered from hepatitis B virus infection.were given telbivudine and pegylated interferon α-2a.After 4 months treatment,both patients developed numbness and pain in the lower limbs.The physical examination showed decreased pain sensation in distal extremities.Hypahidrosis appeared in distal extremities.The nails were pale changed in fingers and toes in cage 1.Case 2 presented mild weakness in the proximal muscle of lower limbs and the tendon reflex was decreased in both lower limbs.His 8erunl creatine kinase level was mild elevated.The electromyography examination and sural nerve biopsies were performed on both patients.Results Electromyography examination showed significant decrease of amplitude of sensory nerve action potentials and mild decrease of sensory nerve conduction velocities in both patients.The amplitude of motor nerve action potentials was also decreased in case 2.Light microscope examination revealed middle reduction of myelinated fibers,wallerian degeneration of myelinated fibers and small clusbers of regenerated fibers in sural nerve.Electro microscopy examination revealed the loss of unmyehnated nerve fibers.After the combined therapy was stopped and vitamin B,CoQ10 and L-camitine were administered,the patients recovered gradually.Conclusions Combined therapy of telbivudine and pegylated interferon α-2a may cause sensory neuropathy with electrophsiological and pathological abnormalities of axonal lesions.The sensory neuropathy induced by the combined therapy may be reversible.     

Combined therapy of telbivudine and pegylated interferon α-2a induced sensory neuropathy:2 case reports

Objective To report the clinical and pathological features of the sensory neuropathy caused by a combined therapy of telbivudine and pegylated interferon α-2a in 2 patients with hepatitis B virus infection Methods Two male patients aged 48(case 1)and 20(case 2),who suffered from hepatitis B virus infection.were given telbivudine and pegylated interferon α-2a.After 4 months treatment,both patients developed numbness and pain in the lower limbs.The physical examination showed decreased pain sensation in distal extremities.Hypahidrosis appeared in distal extremities.The nails were pale changed in fingers and toes in cage 1.Case 2 presented mild weakness in the proximal muscle of lower limbs and the tendon reflex was decreased in both lower limbs.His 8erunl creatine kinase level was mild elevated.The electromyography examination and sural nerve biopsies were performed on both patients.Results Electromyography examination showed significant decrease of amplitude of sensory nerve action potentials and mild decrease of sensory nerve conduction velocities in both patients.The amplitude of motor nerve action potentials was also decreased in case 2.Light microscope examination revealed middle reduction of myelinated fibers,wallerian degeneration of myelinated fibers and small clusbers of regenerated fibers in sural nerve.Electro microscopy examination revealed the loss of unmyehnated nerve fibers.After the combined therapy was stopped and vitamin B,CoQ10 and L-camitine were administered,the patients recovered gradually.Conclusions Combined therapy of telbivudine and pegylated interferon α-2a may cause sensory neuropathy with electrophsiological and pathological abnormalities of axonal lesions.The sensory neuropathy induced by the combined therapy may be reversible.     

Combined therapy of telbivudine and pegylated interferon α-2a induced sensory neuropathy:2 case reports

Objective To report the clinical and pathological features of the sensory neuropathy caused by a combined therapy of telbivudine and pegylated interferon α-2a in 2 patients with hepatitis B virus infection Methods Two male patients aged 48(case 1)and 20(case 2),who suffered from hepatitis B virus infection.were given telbivudine and pegylated interferon α-2a.After 4 months treatment,both patients developed numbness and pain in the lower limbs.The physical examination showed decreased pain sensation in distal extremities.Hypahidrosis appeared in distal extremities.The nails were pale changed in fingers and toes in cage 1.Case 2 presented mild weakness in the proximal muscle of lower limbs and the tendon reflex was decreased in both lower limbs.His 8erunl creatine kinase level was mild elevated.The electromyography examination and sural nerve biopsies were performed on both patients.Results Electromyography examination showed significant decrease of amplitude of sensory nerve action potentials and mild decrease of sensory nerve conduction velocities in both patients.The amplitude of motor nerve action potentials was also decreased in case 2.Light microscope examination revealed middle reduction of myelinated fibers,wallerian degeneration of myelinated fibers and small clusbers of regenerated fibers in sural nerve.Electro microscopy examination revealed the loss of unmyehnated nerve fibers.After the combined therapy was stopped and vitamin B,CoQ10 and L-camitine were administered,the patients recovered gradually.Conclusions Combined therapy of telbivudine and pegylated interferon α-2a may cause sensory neuropathy with electrophsiological and pathological abnormalities of axonal lesions.The sensory neuropathy induced by the combined therapy may be reversible.     

Combined therapy of telbivudine and pegylated interferon α-2a induced sensory neuropathy:2 case reports

Objective To report the clinical and pathological features of the sensory neuropathy caused by a combined therapy of telbivudine and pegylated interferon α-2a in 2 patients with hepatitis B virus infection Methods Two male patients aged 48(case 1)and 20(case 2),who suffered from hepatitis B virus infection.were given telbivudine and pegylated interferon α-2a.After 4 months treatment,both patients developed numbness and pain in the lower limbs.The physical examination showed decreased pain sensation in distal extremities.Hypahidrosis appeared in distal extremities.The nails were pale changed in fingers and toes in cage 1.Case 2 presented mild weakness in the proximal muscle of lower limbs and the tendon reflex was decreased in both lower limbs.His 8erunl creatine kinase level was mild elevated.The electromyography examination and sural nerve biopsies were performed on both patients.Results Electromyography examination showed significant decrease of amplitude of sensory nerve action potentials and mild decrease of sensory nerve conduction velocities in both patients.The amplitude of motor nerve action potentials was also decreased in case 2.Light microscope examination revealed middle reduction of myelinated fibers,wallerian degeneration of myelinated fibers and small clusbers of regenerated fibers in sural nerve.Electro microscopy examination revealed the loss of unmyehnated nerve fibers.After the combined therapy was stopped and vitamin B,CoQ10 and L-camitine were administered,the patients recovered gradually.Conclusions Combined therapy of telbivudine and pegylated interferon α-2a may cause sensory neuropathy with electrophsiological and pathological abnormalities of axonal lesions.The sensory neuropathy induced by the combined therapy may be reversible.     

Peripheral nerves injury of electrophysiology and pathology in MS

OBJECTIVE We report the EMG and pathological features of sural nerve biopsy of 12 patients with MS. The pathological of thesel 1 patients demonstrated demyelination injury of peripheral nerves.METHODS Twelve cases abnomaly are screened with EMG from60 cases MS. Sural nerve biopsy were analyzed by HE AND loyez, and electron microscopy. RESULTS EMG showed slow of MCV in 9 patients and SCV in 7 patients. Myelinated fibers was the presence in 8 sural nerve biopsy patients and most striking demyelinating fibers, regeneration of myelinated fibers. CONCLUSION Ms is characterized by demyelinating disorder limited to the CNS.There are,howeve ,the results of this study sugee that combine with PNS demyelinating injury in MS may be more frequent than is generally assumed.     

Sleeve bridging of the rhesus monkey ulnar nerve with muscular branches of the pronator teres: multiple amplification of axonal regeneration

Multiple-bud regeneration, i.e., multiple amplification, has been shown to exist in peripheral nerve regeneration. Multiple buds grow towards the distal nerve stump during proximal nerve fiber regeneration. Our previous studies have verified the limit and validity of multiple amplification of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple amplification of myelinated nerve fiber regeneration in the primate peripheral nerve. Rhesus monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were sutured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-finger flexion and mild wrist flexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction velocity reached 22.63 ± 6.34 m/s on the affected side of rhesus monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ± 652 in the branches of pronator teres of donor, and 2,661 ± 843 in the repaired ulnar nerve. The rate of multiple amplification of regenerating myelinated nerve fibers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve fibers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple amplification was subsequently detected in ulnar nerve axons.     

Axonal degeneration of the ulnar nerve secondary to carpal tunnel syndrome: fact or fiction?

The distribution of sensory symptoms in carpal tunnel syndrome is strongly dependent on the degree of electrophysiological dysfunction of the median nerve. The association between carpal tunnel syndrome and ulnar nerve entrapment is still unclear. In this study, we measured ulnar nerve function in 82 patients with carpal tunnel syndrome. The patients were divided into group I with minimal carpal tunnel syndrome (n = 35) and group II with mild to moderate carpal tunnel syndrome (n = 47) according to electrophysiological data. Sixty-one age- and sex-matched subjects without carpal tunnel syndrome were used as a control group. There were no significant differences in ulnar sensory nerve peak latencies or conduction velocities from the 4th and 5th fingers between patients with carpal tunnel syndrome and the control group. The ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were lower in patients with carpal tunnel syndrome than in the control group. The ratios of the ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were almost the same in patients with carpal tunnel syndrome as in the control group. These findings indicate that in patients with minimal to moderate carpal tunnel syndrome, there is some electrophysiological evidence of traction on the adjacent ulnar nerve fibers. The findings do not indicate axonal degeneration of the ulnar nerve.     

Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy： an analysis of 500 cases

Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013：221 cases showed symptoms of peripheral neuropathy （symptomatic group） and 279 cases had no symptoms of peripheral impairment （asymptomatic group）. One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases （71.6%）, among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.     

Efficacy of epalrestat plus α-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trials

OBJECTIVE: To evaluate the efficacy of α-lipoic acid(ALA) plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy(DPN). DATA SOURCES: The electronic databases of Pub Med, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were(diabetic peripheral neuropathy or diabetic neuropathy or DPN) AND(α-lipoic acid or lipoic acid or thioctic acid) AND epalrestat. DATA SELECTION: All of the eligible studies met the following inclusion criteria:(1) Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN.(2) The minimum duration of treatment was 2 weeks.(3) The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria.(4) Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. OUTCOME MEASURES: The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity(MNCV), median sensory nerve conduction velocity(SNCV), peroneal MNCV and peroneal SNCV.RESULTS: Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies(RR = 1.29, 95% CI: 1.21–1.38; RR = 1.43, 95% CI: 1.34–1.54, respectively). ALA plus epalrestat combination therapy also significantly improved median MNCV(WMD = 5.41, 95% CI: 2.07–8.75), median SNCV(WMD = 5.87, 95% CI: 1.52–10.22), peroneal MNCV(WMD = 5.59, 95% CI: 2.70–8.47) and peroneal SNCV(WMD = 4.57, 95% CI: 2.46–6.68).CONCLUSION: ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies for clinical efficacy and nerve conduction velocities in patients with DPN.     

Rapid genetic screening of Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies patients

We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an ’onion-like’ structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and ’mouse-nibbled’-like changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced.     

Mild hypothermia for treatment of diffuse axonal injury: a quantitative analysis of diffusion tensor imaging简

Fractional anisotropy values in diffusion tensor imaging can quantitatively reflect the consistency of nerve fibers after brain damage, where higher values generally indicate less damage to nerve fibers. Therefore, we hypothesized that diffusion tensor imaging could be used to evaluate the effect of mild hypothermia on diffuse axonal injury. A total of 102 patients with diffuse axonal injury were randomly divided into two groups: normothermic and mild hypothermic treatment groups. Patient's modified Rankin scale scores 2 months after mild hypothermia were significantly lower than those for the normothermia group. The difference in average fractional anisotropy value for each region of interest before and after mild hypothermia was 1.32–1.36 times higher than the value in the normothermia group. Quantitative assessment of diffusion tensor imaging indicates that mild hypothermia therapy may be beneficial for patients with diffuse axonal injury.     

Comparison of short- with long-term regeneration results after digital nerve reconstruction with musclein-vein conduits

Muscle-in-vein conduits are used alternatively to nerve grafts for bridging nerve defects. The purpose of this study was to examine short- and long-term regeneration results after digital nerve reconstruction with muscle-in-vein conduits. Static and moving two-point discriminations and Semmes-Weinstein Monofilaments were used to evaluate sensory recovery 6–12 months and 14–35 months after repair of digital nerves with muscle-in-vein in 7 cases. Both follow-ups were performed after clinical signs of progressing regeneration disappeared. In 4 of 7 cases, a further recovery of both two-point discriminations and in another case of only the static two-point discrimination of 1–3 mm could be found between the short-term and long-term follow-up examination. Moreover, a late recovery of both two-point discriminations was demonstrated in another case. Four of 7 cases showed a sensory improvement by one Semmes-Weinstein Monofilaments. This pilot study suggests that sensory recovery still takes place even when clinical signs of progressing regeneration disappear.     

Diagnosis and clinical manifestations of subacute combined degeneration of the spinal cord: Analysis of 21 cases

BACKGROUND: Subacute combined degeneration of the spinal cord is caused by vitamin B12 deficiency and is a kind of degenerative disease owing the characteristics of nervous system diseases. In addition, different patients have variously clinical manifestations and various prognoses after vitamin B12 therapy. OBJECTIVE: To investigate and analyze diagnosis, clinical manifestations and prognosis of subacute combined degeneration of the spinal cord. DESIGN: Case analysis. SETTING: Department of Neurology, the Third Hospital of Peking University. PARTICIPANTS: A total of 21 subacute combined degeneration of the spinal cord patients including 14 males and 7 females aged from 33 to 82 years were selected from Department of Neurology, the Third Hospital of Peking University from January 1999 to December 2005. Duration from onset to final diagnosis lasted for 1.5–108 months. All patients had typically clinical manifestations; meanwhile, level of serum vitamin B12 was decreased and/or vitamin B12 therapy was effective. All patients provided the confirmed consent. METHODS: Clinical data of 21 subacute combined degeneration of the spinal cord patients were retrospectively analyzed, while general data and clinical characteristics were recorded at the same time. Levels of blood routine, serum vitamin B12 and homocysteine were measured at the phase of hospitalization. Normal value of serum vitamin B12 was 187–1 059 ng/L and normal value of serum homocysteine was 5–15 μmol/L. All patients received neuroelectrophysiological examination and 15 patients received MRI examinations of spinal cord. After final diagnosis, patients were given vitamin B12 therapy. And follow-up was performed to investigate the prognosis. MAIN OUTCOME MEASURES: ① Levels of blood routine, serum vitamin B12 and homocysteine; ② results of neuroelectrophysiological examination; ③ results of MRI examination of spinal cord; ④ prognosis. RESULTS: Clinical data of 21 patients and follow-up data of 20 patients were involved in the final analysis and 1 patient was lost because of living in the other province. ① Clinical manifestations: All 21 patients had typically clinical manifestations. The original symptoms included numbness of lower and/or upper limbs (5 cases), unstable gait (3 cases), limb asthenia (4 cases), limb numbness combined with light asthenia (5 cases), limb numbness combined with unskillful activity (3 cases), and limb numbness combined with unstable gait (1 case). ② Experimental results: Eight subacute combined degeneration of the spinal cord patients accompanied with mild-severe anemia and mean corpuscular volume of 13 patients were increased. Among 13 subacute combined degeneration of the spinal cord patients not administrating vitamin B12 before hospitalization, the levels of serum vitamin B12 of 2 patients were not measured but those of other patients were decreased. After vitamin B12 therapy,the levels of serum vitamin B12 of 8 patients were normal or increased. In addition, the levels of serum homocysteine of 6 patients were not measured but those of 7 patients were increased. While, the levels of homocysteine of 5 following-up patients were normal. The levels of serum vitamin B12 of 8 patients who received with vitamin B12 therapy before hospitalization were normal or increased. Among them,the levels of homocysteine were not measured in 4 patients, those of 3 patients were increased, and that of 1 patient was normal. ③ Results of neuroelectrophysiological examination: Among all patients, 95% (20/21) patients had abnormal sensory-evoked potential, 89% (8/9) patients had abnormal motor evoked potential, 67% (10/15) patients had abnormal nerve conduction, 13% (2/15) patients had neurogenic muscle injury showed by electromyography (EMG), 70% (7/10) patients had abnormal brain-stem auditory evoked potential, and 40% (4/10) patients had abnormal visual evoked potential. ④ Results of MRI examination of spinal cord: MRI examination demonstrated that 40% (6/15) patients had spinal cord lesion, but spinal cord lesion disappeared in 2 patients during follow up. In addition, clinical manifestations of patients were improved after standard vitamin B12 therapy. CONCLUSION: Nervous system lesion caused by vitamin B12 deficiency is not only involved in spinal cord, also in peripheral nerve, optic nerve, auditory pathway, etc. Diagnosis of the lesion depends on clinical characteristics and level of serum vitamin B12. Especially, neuroelectrophysiological examination, measurement of homocysteine and MRI examination of spinal cord are beneficial for diagnosis and evaluation of therapeutic effects.     

Mild hypothermia combined with a scaffold of NgR- silenced neural stem cells/Schwann cells to treat spinal cord injury

Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor(Ng R)-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly(D,L-lactide-co-glycolic acid)(PLGA) scaffold seeded with Ng R-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the Ng R-silencing cells + PLGA group, hindlimb motor function and nerve electrophysiological function were clearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve fibers were increased in the group treated with the Ng R-silenced cell scaffold + mild hypothermia at 34°C for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviving cells and nerve fibers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with Ng R gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury.     

Autologous transplantation with fewer fibers repairs large peripheral nerve defects

Peripheral nerve injury is a serious disease and its repair is challenging. A cable-style autologous graft is the gold standard for repairing long peripheral nerve defects; however, ensuring that the minimum number of transplanted nerve attains maximum therapeutic effect remains poorly understood. In this study, a rat model of common peroneal nerve defect was established by resecting a 10-mm long right common peroneal nerve. Rats receiving transplantation of the common peroneal nerve in situ were designated as the in situ graft group. Ipsilateral sural nerves(10–30 mm long) were resected to establish the one sural nerve graft group, two sural nerves cable-style nerve graft group and three sural nerves cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long. To reduce the barrier effect due to invasion by surrounding tissue and connective-tissue overgrowth between neural stumps, small gap sleeve suture was used in both proximal and distal terminals to allow repair of the injured common peroneal nerve. At three months postoperatively, recovery of nerve function and morphology was observed using osmium tetroxide staining and functional detection. The results showed that the number of regenerated nerve fibers, common peroneal nerve function index, motor nerve conduction velocity, recovery of myodynamia, and wet weight ratios of tibialis anterior muscle were not significantly different among the one sural nerve graft group, two sural nerves cable-style nerve graft group, and three sural nerves cable-style nerve graft group. These data suggest that the repair effect achieved using one sural nerve graft with a lower number of nerve fibers is the same as that achieved using the two sural nerves cable-style nerve graft and three sural nerves cable-style nerve graft. This indicates that according to the ‘multiple amplification' phenomenon, one small nerve graft can provide a good therapeutic effect for a large peripheral nerve defect.