Distal Sensory Neuropathy Research Articles

Acute Motor Axonal Neuropathy in HIV Infection

To the Editor: Acute motor axonal neuropathy (AMAN)—a variant of Guillian Barre Syndrome (GBS) without sensory involvement has been rarely reported in HIV-infected adults and perhaps never in HIV-infected children. An 11-y-old girl presented with sudden weakness of lower limbs that gradually progressed over three days to involve upper limbs. She had dysentery 20 d back. One year back, she had an attack of Herpes Zoster and was diagnosed to have HIV1 and HIV2 co-infection on ELISA with CD4 count of 853 cells/mm. Both parents had asymptomatic HIV infection. Child was undernourished, weighing 25 kg i.e., < 3rd centile. She had symmetric flaccid quadriparesis with truncal weakness and depressed tendon reflexes. Higher functions and sensory examination were normal. Weakness worsened over next week with complete loss of power in lower limbs but no respiratory or bulbar involvement. CSF and spinal MRI was normal. Stool was negative for poliovirus. Diagnostic tests for C. jejuni were not available. CD4 count was 542 cells/mm. Nerve conduction velocity revealed pure motor axonal neuropathy without demyelination. Patient was treated with intravenous immunoglobulin, following which disease progression stopped but no improvement was noted in muscle power till discharge after one month. Peripheral neuropathies are not uncommon in HIVinfected population, caused by direct viral invasion, immunological dysregulation or antiretroviral drugs, though clinico-pathological spectrum may vary with severity of immunosuppression [1, 2]. Inflammatory demyelinating neuropathies are usually seen during acute seroconversion, while distal sensory neuropathies are commonwith progressive immunosuppression [3]. Neurological complications are suggested to be more common in HIV2 than HIV1 infection, perhaps due to longer survival or higher neurotropism [4]. Present case had combined infection. AMAN is more common in young adults, often following C. jejuni infection. Present case had history of dysentery but confirmation of C. jejuni infection was not possible. Clinical presentation of AMAN in HIV-infected population is same as in others, except longer and severe course or higher recurrence [5]. Diagnosis is supported by nerve conduction studies. Treatment is similar to that in HIV seronegative patients with intravenous immunoglobulins and plasmapheresis being equally effective in hastening recovery, if initiated early.

A case of primary Sjögren'/INS;s syndrome presented with dysautonomia as initial manifestation

Neurological involvement occurs in 10–/INS;42% of the primary Sjö/INS;gren's syndrome (pSS). Distal sensory neuropathy is the most common, pandysautonomia without sensory neuropathy is extremely rare in the pSS as initial manifestation. We describe the case of pSS presented with bladder dysfunction, paralytic ileus and postural intolerance. /INS;A 27-year-old woman developed paresthesia in the both arms 1 week before admission and progressed paresthesia in the legs and trunk below the chest with myalgia. At admission she couldn't urinate and defecate. On examinations she was revealed with /INS;abdominal distension, decreased deep tendon reflexes and sensation for the temperature in the extremities. Autonomic symptoms and signs included no bowel sound during auscultation, increased perspiration on the whole body, bladder distension and postural intolerance with normal pupil sizes and light reflex. Abdomen CT revealed urinary bladder distension and diffuse dilated colon without obstruction suspected paralytic ileus. She had positive anti-SS-A/Ro Ab, anti SS-B/La Ab, positive anti-nuclear antibody (titer 1:40, homogeneous pattern) and anti dsDNA antibody of 38.05 IU, but with negative rheumatoid factor, anti-Sm Ab and Anti-RNP Ab. Salivary scan revealed decreased activity of both the /INS;parotid glands and sublingual glands. Motor and sensory nerve conduction studies of median, ulnar, radial, tibial, peroneal and sural nerves are mild delayed terminal latency with normal amplitude and velocity. During months her symptoms recovered without steroid or IVIG. This case suggests that pSS should be listed in the differential diagnosis of acute autonomic failure as well as chronic form.

Pain, Sleep Disturbances, and Functional Limitations in People Living with HIV/AIDS-Associated Distal Sensory Peripheral Neuropathy

Pain, sleep, and functional disturbances are a common occurrence in people living with HIV/AIDS-related distal sensory peripheral neuropathy (PLWHA-DSPN) yet lack group classification and quantification. A total of 46 PLWHA-DSPN were recruited, as part of a 2-group intervention study, to complete the Neuropathic Pain Scale and the Pittsburgh Sleep Quality Index (PSQI) questionnaires. The participant's performance during a forward reach task and walking distance in 6 minutes was recorded as a measure of function. The pain (60.77 +/- 17.85) and sleep (14.62 +/- 4.28) scores denote marked pain and sleep disturbances, compared to seronegative, age-matched individuals. The ambulation distance was limited (243.99 +/- 141.04 m) and inversely associated with the PSQI-sleep efficiency subscale (rs = -.35, P < .05). The average reaching distances measured (36.07 +/- 7.37 cm) were similar to seronegative, age-matched individuals. Pain, sleep, and functional measures exhibited significant associations. The data collected suggest that PLWHA-DSPN report moderate-to-severe pain and significant sleep disturbances and exhibit limited ambulation distances.

HIV-associated distal neuropathic pain is associated with smaller ventral posterior cingulate cortex

Despite antiretroviral therapy, HIV-associated distal neuropathic pain (DNP) remains one of the most prevalent, disabling and treatment-resistant complications of HIV disease, affecting approximately 20% of patients. Distal sensory neuropathy (DSP) is defined clinically by the presence of abnormal signs on clinical examination. Only a subset of HIV+ individuals with evidence of distal sensory nerve injury by clinical examination experiences DNP. This suggests that some other influence, such as alterations in the CNS processing of afferent sensory information, may modify the phenotypic expression of DSP.

Asymmetrical attenuation of vibration sensation in unilateral diabetic Charcot foot neuroarthropathy

To further characterize the distal sensory neuropathy in subjects with unilateral diabetic Charcot foot neuroarthropathy. A retrospective cohort study to assess the level to which the sensory modalities of pinprick, light touch, vibration, joint position and temperature were attenuated in the affected and unaffected limbs in subjects with unilateral Charcot. The level to which the sensory modality was attenuated in each limb was assigned a score. The Wilcoxon signed rank test was used to compare the scores in the affected and unaffected limbs and also to compare the scores of the different sensory modalities in the affected and unaffected limbs. Fifty subjects with unilateral Charcot foot neuroarthropathy were assessed. Mean age was 45 ± SD 6 years for the 17 subjects with Type 1 diabetes and 62 ± 10 years for the 33 subjects with Type 2 diabetes. Duration of diabetes was 21 ± 13 years, HbA(1c) was 70 ± 19 mmol/mol [8.6 ± 1.8 %] and 15 subjects (30%) required renal replacement therapy. The level of attenuation of vibration sensation was more proximal in the affected compared with the unaffected limbs (P = 0.002). Pinprick, light touch, joint position and temperature sensations were not different. Joint position sensation was less attenuated bilaterally than the other sensory modalities. Asymmetrical attenuation of vibration sensation may predict the side that will develop a Charcot joint and may suggest a more important role for vibration sense loss than loss of other sensory modalities in the pathophysiology of Charcot.

Severe non-opioid-induced pruritus following spinal block

This case report describes an occurrence of intractable localized pruritus after spinal anesthesia in the absence of neuraxial opioid. Pruritus was confined to soles of booth feet. Symptoms were attributed to possible subclinical diabetic distal sensory neuropathy. Pruritus was refractory to IV diphenhydramine, IV lidocaine but responded quickly to subhypnotic dose of IV propofol. The close relationship between pathways for pain and pruritus may result in severe and unusual symptoms. Diagnostic workup should include tests for distal sensory neuropathy. Further understanding of neuropathic pruritus is needed.

Sensory Neurons Derived from Diabetic Rats Have Diminished Internal Ca2+ Stores Linked to Impaired Re-uptake by the Endoplasmic Reticulum

Distal symmetrical sensory neuropathy in diabetes involves the dying back of axons, and the pathology equates with axonal dystrophy generated under conditions of aberrant Ca2+ signalling. Previous work has described abnormalities in Ca2+ homoeostasis in sensory and dorsal horn neurons acutely isolated from diabetic rodents. We extended this work by testing the hypothesis that sensory neurons exposed to long-term Type 1 diabetes in vivo would exhibit abnormal axonal Ca2+ homoeostasis and focused on the role of SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase). DRG (dorsal root ganglia) sensory neurons from age-matched normal and 3–5-month-old STZ (streptozotocin)-diabetic rats (an experimental model of Type 1 diabetes) were cultured. At 1–2 days in vitro an array of parameters were measured to investigate Ca2+ homoeostasis including (i) axonal levels of intracellular Ca2+, (ii) Ca2+ uptake by the ER (endoplasmic reticulum), (iii) assessment of Ca2+ signalling following a long-term thapsigargin-induced blockade of SERCA and (iv) determination of expression of ER mass and stress markers using immunocytochemistry and Western blotting. KCl- and caffeine-induced Ca2+ transients in axons were 2-fold lower in cultures of diabetic neurons compared with normal neurons indicative of reduced ER calcium loading. The rate of uptake of Ca2+ into the ER was reduced by 2-fold (P<0.05) in diabetic neurons, while markers for ER mass and ER stress were unchanged. Abnormalities in Ca2+ homoeostasis in diabetic neurons could be mimicked via long-term inhibition of SERCA in normal neurons. In summary, axons of neurons from diabetic rats exhibited aberrant Ca2+ homoeo<1?show=[fo]?>stasis possibly triggered by sub-optimal SERCA activity that could contribute to the distal axonopathy observed in diabetes.

Tolerability of NGX-4010, a capsaicin 8% patch for peripheral neuropathic pain

Background/purposeNGX-4010 (QUTENZA™; NeurogesX Inc, San Mateo, CA), a capsaicin 8% dermal patch, is licensed in the European Union for the treatment of peripheral neuropathic pain (PNP) in nondiabetic adults and in the United States for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN). While NGX-4010 treatment is associated with a low risk of systemic adverse events, patch application-related pain is common and may be managed with local cooling and/or oral analgesics. This article characterizes the tolerability of NGX-4010 and will help to guide any pain management.MethodsThis integrated analysis of tolerability data collected from the NGX-4010 clinical study program included 1696 patients with PNP. Patch application-related pain on the treatment day was captured as Numeric Pain Rating Scale (NPRS) “pain now” scores while “average pain for the past 24 hours” NPRS scores were analyzed for 7 days following treatment. Other tolerability assessments included the percentage of patients completing ≥90% of the intended treatment duration and patients using medication for patch application-related pain.ResultsThe mean maximum change in “pain now” NPRS scores from pretreatment levels during and after patch application was 2.6 for all patients. This pain was transient and resolved following patch removal. Mean “average pain for the past 24 hours” NPRS scores returned to baseline by the evening of the treatment day for patients with PHN, and the evening of day 2 for patients with human immunodeficiency virus-associated distal sensory polyneuropathy or painful diabetic neuropathy. Repeated NGX-4010 applications did not affect the intensity of patch application-related pain. Almost all patients (≥98%) completed ≥90% of the full treatment duration, regardless of the number of treatments received.ConclusionTransient patch application-related pain with NGX-4010 can be managed with local cooling and/or oral analgesics in nearly all cases. Patient adherence to the full intended treatment duration indicated that patch application-related pain was not a barrier to NGX-4010 use.

Spontaneous rupture of the peroneus longus tendon in a patient with diabetic sensory neuropathy

AbstractWe present a case of spontaneous painless rupture of the peroneus longus tendon in a patient with poorly controlled type 2 diabetes and a distal sensory neuropathy. Tendon rupture in the diabetic neuropathic foot has been previously described, but not of the peroneus longus tendon.Painless tendon rupture in the diabetic foot or ankle can present a diagnostic challenge, and requires a high index of suspicion. Copyright © 2011 John Wiley &amp; Sons.

Efficacy of Stability Trainer in Improving Balance in Type II Diabetic Patients with Distal Sensory Neuropathy

Efficacy of Stability Trainer in Improving Balance in Type II Diabetic Patients with Distal Sensory Neuropathy

POI12 Electrophysiological sensory demyelination in typical chronic inflammatory demyelinating polyneuropathy

BackgroundElectrophysiological demyelination of sensory nerves is not routinely assessed in the evaluation of suspected chronic inflammatory demyelinating polyneuropathy (CIDP). Its usefulness is unknown.MethodsWe compared in 19 patients with typical chronic...

POG04 Multiple mitochondrial DNA deletions, cyclooxygenase-negative fibres and slowly progressive cognitive decline with psychiatric features

BackgroundMultiple deletions of mitochondrial DNA (mtDNA) arising from nuclear gene defects underlie a spectrum of disorders ranging from the severe Alpers syndrome to mild cases of progressive external ophthalmoplegia. Cognitive...

European Federation of Neurological Societies/Peripheral Nerve Society Guideline* on management of paraproteinemic demyelinating neuropathies. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revision

The aim of this guideline is to update the 2006 EFNS/PNS guideline on management of patients with a demyelinating neuropathy and a paraprotein (paraproteinemic demyelinating neuropathy [PDN]) by review of evidence and expert consensus. In the absence of adequate evidence, the panel agreed on good practice points: (1) patients with PDN should be investigated for a malignant plasma cell dyscrasia; (2) a monoclonal gammopathy of undetermined significance is more likely to be causing the neuropathy if it is immunoglobulin (Ig)M, anti-neural antibodies are present, and the clinical phenotype is chronic distal sensory neuropathy; (3) patients with IgM PDN usually have predominantly distal sensory impairment, prolonged distal motor latencies, and often anti-myelin-associated glycoprotein antibodies; (4) IgM PDN may respond to immunomodulatory therapies. Their potential benefit should be balanced against possible side effects and the usually slow disease progression; (5) IgG and IgA PDN may be indistinguishable from chronic inflammatory demyelinating polyradiculoneuropathy; and (6) Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes syndrome is a multi-system malignant PDN.

Electrophysiological sensory demyelination in typical chronic inflammatory demyelinating polyneuropathy

The presence of electrophysiological demyelination of sensory nerves is not routinely assessed in the evaluation of suspected chronic inflammatory demyelinating polyneuropathy (CIDP). Whether this can be useful is unknown. We compared, using surface recording techniques, in 19 patients with typical CIDP and 26 controls with distal large fibre sensory axonal neuropathy, the forearm median sensory conductions, sensory nerve action potential (SNAP) amplitudes and durations and sensory nerve conduction velocities (SNCVs) of median, radial and sural nerves. Median nerve sensory conduction block (SCB) across the forearm was greater in CIDP patients than in controls (P = 0.005). SNAP durations were longer in CIDP patients for median (P = 0.001) and sural nerves (P = 0.004). Receiver operating characteristic (ROC) curves provided sensitive (>40%) and specific (>95%) cut-offs for median nerve SCB as well as median and sural SNAP durations. SNCVs were significantly slower for median and sural nerves in CIDP patients, but ROC curves did not demonstrate cut-offs with useful sensitivities/specificities. Median SCB or prolonged median SNAP duration or prolonged sural SNAP duration offered a sensitivity of 73.7% for CIDP and specificity of 96.2%. Used as additional parameters, they improved diagnostic sensitivity of the American Academy of Neurology (AAN) criteria for CIDP of 1991, from 42.1% to 78.9% in this population, with preserved specificity of 100%. Sensory electrophysiological demyelination is present and may be diagnostically useful in typical CIDP. SCB detection and SNAP duration prolongation appear to represent more useful markers of demyelination than SNCV reduction.

Emergent T‐helper 2 profile with high interleukin‐6 levels correlates with the appearance of bortezomib‐induced neuropathic pain

Emergent T‐helper 2 profile with high interleukin‐6 levels correlates with the appearance of bortezomib‐induced neuropathic pain

The Clinical Spectrum of Neurological Manifestations in HIV/AIDS Patients on HAART at the Lagos University Teaching Hospital, Lagos, Nigeria

The human immunodeficiency virus (HIV) is primarily neurotrophic and lymphotrophic. Diverse neurologic sequealae have been documented with variations based on disease severity, but geographic variation may determine the distribution of these neurological complications. This study was designed to evaluate the current status of neurologic manifestations of HIV/AIDS as seen at our tertiary referral centre in Lagos, Nigeria. Consecutively presenting persons with HIV/ AIDS receiving HAART, who were seen between August 2004 and March 2006 at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria, were recruited into the study. Two hundred and fifty consecutively presenting HIV sero-positive patients were seen. There were 102 males (40.8%) and 148 females (59.2%) with a mean age of 37.4 years. 86 (34.4%) had clinically evident neurological disease, including neurocognitive dysfunction in 65 (53%), distal sensory neuropathy in 41 (16.4%), meningitis in 16 (6.4%), myopathy in 13 (5.2%), myelopathy in 6 (2.4%) and cerebrovascular disease in 5 (2%). The mean CD4 count (cells/mm3) of patients with neurological disease, 201.1 +/- 124.8 was significantly lower than that of patients without neurological disease 253.5 +/-149.2 (P = 0.001). Clinically evident neurological disease occurs in about 1/3rd of patients with HIV/AIDS on HAART at our tertiary centre, and predominantly affects patients with more advanced disease stages evidenced by lower CD4 count.

Reliability of Superficial Peroneal, Sural, and Medial Plantar Nerve Conduction Studies

The reliability of medial plantar, sural, and superficial peroneal nerve conduction studies (NCS) has not been widely studied. These nerves are usually involved in distal sensory neuropathies and their serial study is relevant in the clinical setting. To determine the inter- and intrarater reliability of superficial peroneal, sural, and medial plantar NCS in healthy participants. Two raters performed the bilateral NCS twice in 20 healthy participants (23.5 +/- 3.5 years). Reliability was analyzed by the Bland-Altman method and intraclass correlation coefficient (ICC). Variability was established by the coefficient of variation. The Bland-Altman method showed a good level of intra- and interrater agreement for all nerves. The amplitude (rater 1) and latency of the medial plantar nerve and the amplitude of the sural nerve (rater 2) had an intrarater ICC of >or=0.75. Interrater analysis showed concordance levels between moderate and very low. The highest coefficients of variations were found for amplitude and the lowest for nerve conduction velocity. Although the Bland-Altman method confirmed a good intra- and interrater reliability of the studied nerves, ICC analyses showed mixed results. These statistical approaches are complementary, and each one has advantages and disadvantages that must be considered in their application and interpretation.

Postpartum relapsing sensory neuritis responsive to intravenous immunoglobulin

Sirs, Pure sensory vasculitic neuropathy has been described but is rare [2, 3]. Randomised controlled trial data is lacking, however treatment with various immunosuppressants has been suggested [1]. Postpartum relapses of sensory vasculitic neuropathy have not been described. We report a case of postpartum relapsing vasculitic sensory neuropathy exquisitely responsive to intravenous immunoglobulin (ivIg) with a benign course despite severe endstage features on nerve biopsy. A 27-year-old woman developed a rapidly progressive burning sensation in both feet during the seventh month of her second pregnancy. Two days following delivery of a healthy baby, she was unable to walk and required opiate analgesics for pain control. Examination revealed diminished pinprick and vibration in both feet as well as absent ankle reflexes, however wasting and weakness were not present. Nerve conduction studies (NCS) confirmed a distal sensory neuropathy. Investigations for systemic vasculitis were negative. The patient was given ivIg 0.4 g/kg/day for 5 days on six occasions 6 weeks apart. Her painful sensory symptoms started to improve and she was able to walk by the end of the first week of treatment. By the end of the second cycle of ivIg she was able to discontinue opiates. Subsequently there was gradual improvement in her symptoms, with complete resolution of symptoms by the end of the fourth cycle of ivIg. The patient remained well for 3 years but shortly after the birth of her third child the painful sensory symptoms recurred. Again, the patient’s symptoms responded well to six cycles of ivIg at a dose of 0.4 g/kg/day for 5 days at 6-weekly intervals, with a similar pattern of response as on the first occasion. Examination findings remain unchanged, without evidence of wasting or weakness. Sural nerve biopsy showed perivascular lymphocytic infiltration around in the epineurium with transmural migration of lymphocytes and partial obstruction of vessel walls (Fig. 1a, b). There was almost complete loss of myelinated fibres (Fig. 1c). The appearances were consistent with a severe end-stage vasculitic neuropathy. NCS were repeated 4 years after initial presentation and did not show any significant deterioration compared with the initial studies (Table 1). Distal, symmetric sensory neuropathy secondary to nonsystemic vasculitis [2] is rare but may show a benign course [3]. Randomised controlled trials of therapy in nonsystemic vasculitic neuropathy have not been carried out [3], but anecdotal case series suggest treatment with immunosuppressive therapies such as cyclophosphamide, azathioprine and steroids [1]. Postpartum relapsing vasculitic sensory neuropathy has not been described to our knowledge, although postpartum relapses have been described in systemic vasculitides [4]. This patient demonstrated a dramatic response to ivIg, with prolonged periods of remission after each course of treatment and has not accumulated any functional disability despite the severity of the nerve biopsy findings. She has elected not to have further children due to the perceived risk of relapse. S. M. Murphy (&) M. J. Hennessy Department of Neurology, Galway University Hospital, Newcastle Road, Galway, Ireland e-mail: smurph1@hotmail.com

Effects of active HCV replication on neurologic status in HIV RNA virally suppressed patients

Hepatitis C virus (HCV) is a frequent copathogen with HIV. Both viruses appear to replicate in the brain and both are implicated in neurocognitive and peripheral neuropathy syndromes. Interaction of the viruses is likely to be complicated and better understanding of the contributions of each virus will be necessary to make evidence-based therapeutic decisions. This study was designed to determine if active HCV infection, identified by quantitative HCV RNA determination, is associated with increased neurocognitive deficits or excess development of distal sensory peripheral neuropathy in HIV coinfected patients with stable HIV viral suppression. The AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) study was the source of subjects with known HIV treatment status, neurocognitive and neuropathy evaluations, and HCV status. Subjects were selected based on HCV antibody status (249 positive; 310 negative). HCV RNA viral loads were detectable in 172 participants with controlled HIV infection and available neurologic evaluations in the ALLRT. These participants were compared with 345 participants with undetectable HCV viral load and the same inclusion criteria from the same cohort. Neurocognitive performance measured by Trail-Making A or B and digit symbol testing was not dissimilar between the 2 groups. In addition, there was no significant association between active HCV replication and distal sensory neuropathy. Clinically significant neurocognitive dysfunction and peripheral neuropathy were not exacerbated by active hepatitis C virus infection in the setting of optimally treated HIV infection.

Distal Sensory Peripheral Neuropathy in HIV: A Case Study

Distal sensory peripheral neuropathy (DSP) is a common problem experienced with the human immunodeficiency virus (HIV). The pain associated with DSP can be severe and debilitating. Interventions used to manage DSP related to HIV have been adopted from the medical management of peripheral neuropathy secondary to diabetes. However, foot care recommendations for HIV and DSP have not been instituted unlike the diabetes literature. This article illustrates the clinical and the educational needs of individuals with HIV and DSP.