Severe Sensory Neuropathy Research Articles

Laughing gas abuse causing subacute combined spinal cord degeneration with psychiatric manifestations

Background. Nitrous oxide, a nonirritating gas commonly used as an anesthetic, is increasingly abused by the young population for its euphoric effects due to its seemingly harmless nature. However, its neurological impacts can vary in intensity and sometimes result in permanent damage. Accurate diagnosis and treatment hinge on identifying nitrous oxide use through anamnesis, clinical and paraclinical findings, as demonstrated in the following case report. Case report. A 27-year-old female with psychiatric history presented with progressive paresthesia and walking difficulty, admitting to recent nitrous oxide use, alongside other substances. Clinical examination revealed mild tetraparesis, coordination disturbances, generalized hyporeflexia, and sensory deficits. Electromyography showed severe sensory neuropathy, and spinal MRI indicated subacute combined degeneration (SCD) of the spinal cord. Laboratory tests revealed hyperhomocysteinemia and elevated methylmalonic acid levels, despite normal vitamin B12 levels. Treatment included intramuscular vitamin B12, folic acid, and neurotrophic agents, along with physical rehabilitation. Psychiatric symptoms, possibly exacerbated by nitrous oxide, and complicated adherence to therapy. Conclusions. This case underscores the neurotoxic potential of nitrous oxide, particularly its disruption of cobalamin metabolism, and highlights the need for thorough patient histories to uncover substance use contributing to neurological symptoms. Despite treatment, some neurological deficits may persist, emphasizing the importance of early intervention and comprehensive care strategies.

Nerve ultrasound in Friedreich’s Ataxia: enlarged nerves as a biomarker of disease severity

ObjectiveIn Friedreich's ataxia research, the focus is on discovering treatments and biomarkers to assess disease severity and treatment effects. Our study examines high-resolution nerve ultrasound in these patients, seeking correlations with established clinical markers of disease severity. MethodTen patients with Friedreich’s Ataxia underwent a comprehensive clinical assessment with established scales (SARA, FARS, mFARS, INCAT, ADL 0-36, IADL). Additionally, they underwent nerve conduction studies and high-resolution nerve ultrasound. Quantitative evaluation of nerve cross-sectional area, conducted at 24 nerve sites using high-resolution nerve ultrasound, was compared with data obtained from 20 healthy volunteers. ResultsAll the patients had a severe sensory axonal neuropathy. High-resolution nerve ultrasound showed significant increase, in cross sectional area, of median and ulnar nerves at the axilla and arm. The cumulative count of affected nerve sites was directly associated with clinical disability, as determined by SARA, FARS, mFARS, ADL 0-36, and INCAT score, while displaying an inverse correlation with IADL. ConclusionsOur study shows that high-resolution ultrasound reveals notable nerve abnormalities, primarily in the upper limbs of patients diagnosed with Friedreich’s Ataxia. The observed correlation between these nerve abnormalities and clinical disability scales indicates the potential use of this technique as a biomarker for evaluating disease severity and treatment effects. SignificanceNerve Ultrasound is a potential biomarker of disease severity in Friedreich’s Ataxia.

A Case of Acute Motor Sensory Axonal Neuropathy, a Rare Form of Guillain-Barre Syndrome, Developing After Multiple COVID-19 Infections (P13-8.009)

<h3>Objective:</h3> Guillain-Barre syndrome (GBS), an autoimmune polyneuropathy characterized by ascending weakness and characteristic cerebrospinal fluid (CSF) findings, has been identified in patients previously diagnosed with COVID-19, treated for COVID-19 infection, or vaccinated against the same. GBS is divided into axonal and demyelinating subtypes, and confirmatory testing such as electromyography and nerve conduction studies can help differentiate between subtypes. Here we present a case with recurrent COVID-19 infections, most recently treated with bebtelovimab, who developed acute motor sensory axonal neuropathy (AMSAN), a rare variant of axonal GBS. <h3>Background:</h3> A 33-year-old female presented with progressive ascending weakness and sensory loss that started two weeks after COVID-19 infection. She was fully vaccinated, however, had four episodes of COVID-19 infection within the past year and a half. Two weeks after the most recent infection, which was treated with bebtelovimab, she developed rapidly progressive weakness and sensory impairment in bilateral lower extremities quickly involving upper extremities. She received two rounds of intravenous immunoglobulin (IVIG) three and five weeks after symptoms onset. Her symptoms continued to progress requiring hospitalization. Exam showed severe weakness in all limbs with distal muscle atrophy in upper extremities. Imaging was negative. CSF demostrated albuminocytological dissociation. Nerve conduction studies concluded severe motor and sensory axonal neuropathy with active denervation which led to the suspicion of Acute Motor and Sensory Axonal Neuropathy (AMSAN), a rare variant of GBS. She underwent plasmapheresis with only minimal improvement. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> Many cases of GBS have been reported after COVID-19 infection but only a few of them are about AMSAN. This case presents unique features including multiple COVID-19 infections despite prior vaccination, and the development of this rare variant of GBS. It raises the concern of multiple COVID-19 infections having a cumulative impact on peripheral nervous system leading to more severe forms of GBS with poor response to treatment. <b>Disclosure:</b> Dr. Narvaez Caicedo has nothing to disclose. Mr. Rao has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Wu has nothing to disclose.

The Neuroanatomical Basis of Unfamiliar Presentations of Herpes Zoster: A Review and A Case Report

Herpes zoster (HZ, shingles) is caused by reactivated varicella zoster virus, that travels along the peripheral branches from its dormant location in neurons of spinal and cranial sensory ganglia. HZ is well known for its skin vesicular eruptions and severe sensory neuropathy. Over the years, reports have described the occurrence of segmental paresis of skeletal muscles and the involvement of the large and small intestine, clinically resembling intestinal obstruction.

A SUCCESSIVE CLINICAL STORY ON GUILLAIN-BARRE SYNDROME UNDER THE LIGHT OF AYURVEDA: A CASE STUDY

Guillain-Barre syndrome (GBS) is a group of autoimmune syndromes comprising the disease's demyelinating and acute axonal degenerating forms. It is also an acute-onset, monophasic, immune-mediated polyneuropathy that often follows an antecedent infection. Here is an interesting case study where a 16-year-old girl with her parents reported to the outpatient department with the chief complaint of inability to walk without support, weakness in bilateral calf muscles, weakness in bilateral upper limbs and lower limbs and tingling sensation, pulling type of pain in the right ankle joint and also the heaviness of bilateral lower limbs, more in the morning. By examination, her sensory and motor systems showed impairment; one was hypotonic, proprioception was affected, and her gait was a high steppage gait. Her assessment was done by using Hughes GBS Disability Scale- 3/6. The patient’s nerve conduction study revealed severe motor and sensory axonal neuropathy in the upper and lower limbs. By seeing the nature of the disease and the patient's symptoms, we correlated with sarvanga vata according to our classics. Treatments were koshta shodhana (gut cleansing), abhyanga (massage of the whole body with medicated oil), Shastikashali panda sweda (Rubbing of medicated rice poultice over the body), basti (transrectal administration of medicines) and oral medicaments. Panchakarma treatments were for 30 days, followed by oral medications for the next 140 days. The intervention period of 154 days showed complete recovery of all the motor and sensory deficits; however, follow-up of the patient was maintained for 269 days, looking into the sustainability of the outcomes.

HP41: Idiopathic systemic capillary leak syndrome with severe peripheral nervous system involvement. Case report

Idiopathic systemic capillary leak syndrome (ISCLS) a rare condition characterised by repeated relapses of leaking of plasma from blood vessels into body cavities and muscles. In one third of cases the disease is associated with variable severity peripheral nervous system damage. 26 years old male was admitted to hospital after repeated fainting with complains about progressive pain and numbness in lower limbs. In the hospital symptoms were rapidly progressing and patient developed asymmetrical painful tetraparesis (muscle strength in legs 0-1, muscle strength in arms 4). Systemic manifestations included hypotension, tachycardia, hemoconcentration, hypoalbuminemia, cardiac tamponade, crush syndrome. On 5th day from symptom onset treatment with intravenous immunoglobulin (IvIg) was started. After first IVIG treatment course systemic symptoms had resolved. Patient continued to receive IvIg monthly as a prophylactic treatment. After two courses of IvIg pain ceased, muscle strength improved (arm muscles 5, leg muscles 4). Patient died 20 months after symptom onset due to repeated systemic relapses. Electrodiagnostic study (EMG/NCS) was performed 3 times (on 3rd day from symptom onset, after first and second IvIg course). First EMG/NCS showed severe axonal motor and sensory neuropathy in legs, mild motor axonal damage in arms with massive spontaneous activity in all examined muscles. After repeated IvIg courses NCS in arms become normal, in legs tibial and peroneal MUAP remained absent, sural SNAP became normal; EMG showed slight evidence of reinnervation process without signs of active denervation. Conclusion. ISCLS can be considered in patients with rapidly progressive axonal polyradiculoneuritis with autonomic signs.

ACUTE MOTOR SENSORY AXONAL NEUROPATHY (AMSAN) VARIANT OF GUILLIAN BARRE SYNDROME (GBS) COMPLICATING PREGNANCY: A CASE REPORT

INTRODUCTION: Guillain Barre Syndrome (GBS), is an autoimmune disorder which manifests as Polyradiculoneuropathy(1,2). Several variants of GB have been identied of which Acute Motor Axonal Neuropathy (AMAN) and Acute Motor and Sensory Axonal Neuropathy (AMSAN) variants mainly occur by demyelination of neurons induced by inammation. CASE REPORT: A 20 Year old primigravida at 28 weeks of gestation, presented with history of weakness of all four limbs since 2 months. Nerve Conduction study showed evidence of Severe motor and sensory axonal neuropathy. Patient was managed with corticosteroids and showed improvement in her symptoms during her stay in the hospital. CONCLUSION: AMSAN a rare variant of GBS is uncommon in pregnancy and it can be associated with severe morbidity and complications if unrecognized and if not treated early. Such patients should be diagnosed early and should be given a multidisciplinary care and promptly treated. Prompt and early diagnosis of AMSAN variant of GBS , with a team effort involving the Physician, the Neurologist and the Obstetrician, along with an early initiation of immune-modulatory therapy, it can be ensured that good outcomes can be expected from both the mother and the fetus.

Development of a prediction model for foot ulcer recurrence in people with diabetes using easy-to-obtain clinical variables

IntroductionWe aimed to develop a prediction model for foot ulcer recurrence in people with diabetes using easy-to-obtain clinical variables and to validate its predictive performance in order to help risk...

Teaching Video NeuroImage: Choreoathetosis and Focal Dystonia in Vitamin B12 Deficiency.

An 87-year-old man presented with involuntary movements of his fingers for 3 months. Clinical examination showed dystonia with choreoathetosis of his hands and fingers (Video 1). Pinprick sensation was reduced to ankles and vibration sense was absent up to shoulders and costal margin bilaterally. Investigations revealed hemoglobin of 10.1 g/dL, mean corpuscular volume of 94.6 fL, vitamin B12 level of <92 pmol/L, and the presence of antiparietal cell antibody. He was diagnosed with pernicious anemia and treated with intramuscular cyanocobalamin (1,000 μg weekly for 4 weeks then monthly). Reassessment 2 months later showed significant clinical improvement and normalized vitamin B12 level of 534 pmol/L. Pseudoathetosis—a slow, writhing movement of the distal extremities seen in severe sensory neuropathy—was also considered. However, the patient's movements did not worsen with eye closure. Severe vitamin B12 deficiency may result in chorea, myoclonus, tremor, and dystonia.1 These manifestations, possibly a result of basal ganglia dysfunction, are rare but important to recognize as they are largely reversible with supplementation.2

Health-Related Quality of Life With Trastuzumab Monotherapy Versus Trastuzumab Plus Standard Chemotherapy as Adjuvant Therapy in Older Patients With HER2-Positive Breast Cancer.

We report findings on quality of life (QoL) in the RESPECT trial, which compared adjuvant trastuzumab monotherapy with trastuzumab plus chemotherapy in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). Patients age 70-80 years with human epidermal growth factor receptor 2-positive surgically treated breast cancer were randomly assigned to receive trastuzumab (T) or trastuzumab plus chemotherapy (T + C). QoL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G), Philadelphia Geriatric Center Morale Scale, Hospital Anxiety and Depression Scale, Patient Neurotoxicity Questionnaire, and Tokyo Metropolitan Institute of Gerontology Index of Competence at baseline and after 2, 12, and 36 months. Comparisons were based on individual changes from baseline and were performed by Fisher's test or mixed-model repeated-measures. Among 275 patients in the parent study, 231 (84%) (average age: 74 years) were included in the analysis. At 2, 12, and 36 months, 198, 177, and 178 patients completed surveys, and the mean FACT-G scores at each survey point were 78.9, 80.4, 82.7, and 79.1 in group T and 79.5, 74.5, 78.4, and 78.5 in group T + C. Compared with group T + C, the proportion of patients showing QoL deterioration (≥ 5 points decrease from baseline in FACT-G) was significantly lower at 2 months (31% v 48%; P = .016) and 12 months (19% v 38%; P = .009). In group T, the Hospital Anxiety and Depression Scale score (P = .003) and the proportion of severe sensory peripheral neuropathy (P = .001) were significantly lower at 2 months, and Philadelphia Geriatric Center Morale Scale and Tokyo Metropolitan Institute of Gerontology Index of Competence scores were significantly higher (P = .024, .042) at 12 months. At 36 months, there were no significant differences in any QoL items. Detrimental effects of adjuvant chemotherapy on global QoL, morale, and activity capacity lasted for at least 12 months but were not observed at 36 months.

De novo DNM1L variant presenting with severe muscular atrophy, dystonia and sensory neuropathy

DNM1L encodes dynamin-related protein 1 (DRP1), a multi-domain GTPase essential for mitochondrial and peroxisomal division. Autosomal dominant and recessive variants in DNM1L cause encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1), which presents as a complex and clinically heterogeneous neurological disorder of variable severity, often accompanied by seizures. Clinical features are diverse, and no clear phenotype-genotype correlations were drawn to date. DNM1L-related sensory neuropathy has recently been reported as a predominant feature in one case with a de novo variant in the GTPase domain. Herein we present a second case with DNM1L-related sensory neuropathy as the predominant underlying feature without motor neuron involvement, which resulted in severe muscular atrophy and generalized dystonia.

EP35 Cryoglobulinaemic vasculitis: an uncommon complication of Sjögren’s syndrome

EP35 Cryoglobulinaemic vasculitis: an uncommon complication of Sjögren’s syndrome

High glucose level as a modifier factor in CMT1A patients.

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common type of hereditary neuropathy worldwide and diabetes mellitus (DM) is the most frequent cause of peripheral neuropathy in the Western world. CMT1A typically manifest as a predominant motor neuropathy, while, DM-related neuropathy often manifests as a predominant sensory disorder. There are some evidences that CMT1A patients that also had DM had a more severe neuropathy. Although the real frequency and the underlying mechanisms related to this association has not yet been addressed in the literature. We sought to characterize the phenotypic variability of CMT1A patients with persistent high glucose levels (DM or impaired glucose tolerance [IGT]). Nineteen patients with CMT1A and DM (CMTdiab), seven with CMT1A and IGT (CMTintol) and 27 with CMT1A without comorbidities were analyzed. They were evaluated through clinical assessment, application of the following scales: visual analogue scale, McGill, CMTNS, SF-36 and COMPASS 31 and electrophysiological studies. Patients CMTdiab had a more severe motor and sensory neuropathy, more intense autonomic symptoms and worse quality of life. Surprisingly, proximal weakness and temporal dispersion on nerve conduction studies are frequently observed in this group. Patients CMTintol also had a more severe neuropathy. Curiously, we observed that the association of CMT1A and glucose metabolism disorders (CMTglic) clustered in some families. Patients CMTglic develop a more severe neuropathy. As there is yet no cure to CMT1A, a strict blood sugar control may be a useful measure.

Abstract PD10-02: Patient reported outcomes from the adjuvant trastuzumab emtansine (T-DM1) vs. paclitaxel + trastuzumab (TH) (ATEMPT) trial (TBCRC 033)

Abstract Purpose: The ATEMPT trial sought to determine if adjuvant T-DM1 (every 3 wks for 1 yr) for Stage I HER2 positive breast cancer is better tolerated than TH (paclitaxel weekly x 12 wks with 1 yr of trastuzumab). Here we compare patient-reported outcomes (PROs) including quality of life (QOL), specific symptoms, and work productivity between the two treatments over time. Patients and Methods: English-speaking patients were randomized (3:1) to T-DM1 or TH, and completed PRO assessments at baseline (day 1), 3 wks, 12 wks, and 6, 12, and 18 mos after initiation of treatment. Surveys included the FACT-B, Patient-Neurotoxicity Questionnaire (PNQ), Rotterdam Symptom Checklist (RSCL), Alopecia Patient Assessment, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). Results: 469/497 (94%) patients (363 on T-DM1, 106 on TH) completed surveys at any timepoint, ranging from 100% at baseline to 79% at 18 mos. Median age was 56 yrs (range 23-85). There were different patterns of deterioration and recovery seen over time in each group for QOL and other relevant symptoms. Compared with the T-DM1 group, the TH group had significantly lower mean total FACT-B scores, indicating poorer QOL from baseline to 12 weeks (p&amp;lt;0.001 for each timepoint); mean scores were similar between the groups at 6 and 12 mos, and significantly worse again in the TH group at 18 mos. The greatest mean change from baseline, and lowest FACT-B scores overall were reported in the TH group at 12 weeks. Moderate to severe sensory neuropathy was 8% at 12 weeks for patients receiving T-DM1 and reached its highest level of 15% by 18 mos. In comparison, moderate to severe sensory neuropathy was 35% at 12 weeks and 26% at 18 mos for patients on TH (p&amp;lt;0.001 at 12 weeks and p=0.018 at 18 mos). Hair loss at week 12 was 13% on T-DM1 compared to 77% on TH (p&amp;lt;0.001). Mean physical symptom distress was greater for TH at baseline, 3 and 12 weeks, and greater for T-DM1 at 1 year, with greatest symptom distress reported by the TH group at 12 weeks. Psychological distress was greatest for both groups at enrollment, though significantly greater with TH than T-DM1 at baseline, 12 weeks and 18 mos (groups were similar at 6 and 12 mos). There was limited impact on activity level impairment in both groups. Rates of employment were lowest for the TH group at 12 weeks (49% TH vs. 61% T-DM1, p=0.074) with significant differences seen at 3 and 12 weeks for percent work time missed due to health treatment, percent impairment while working, percent overall work impairment, and percent activity impairment, all favoring T-DM1. Conclusion: PROs differ between patients with Stage I HER2 positive breast cancer treated with T-DM1 vs. TH. T-DM1 treated patients had better QOL, less neuropathy and hair loss, and better work productivity, particularly during the first 12 weeks of treatment, and importantly, differences persist with longer-term follow-up. Citation Format: Ann Partridge, Yue Zheng, Shoshana Rosenberg, Richard Gelber, Shari Gelber, William Barry, Chau Dang, Denise Yardley, Steven Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, Ron Bose, Douglas Weckstein, Antonio Wolff, Katherine Reeder-Hayes, Hope Rugo, Bhuvaneswari Ramaswamy, Dan Zuckerman, Lowell Hart, Vijayakrishna Gadi, Michael Constantine, Kit Cheng, Frederick Briccetti, Bryan Schneider, Merrill Garrett, P. Kelly Marcom, Kathy Albain, Patricia Defusco, Nadine Tung, Blair Ardman, Rita Nanda, Rachel Jankowitz, Michelle DeMeo, Harold Burstein, Eric P. Winer, Ian Krop, Sara Tolaney. Patient reported outcomes from the adjuvant trastuzumab emtansine (T-DM1) vs. paclitaxel + trastuzumab (TH) (ATEMPT) trial (TBCRC 033) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-02.

Irreversible neuropathy in extremely-drug resistant tuberculosis: An unfortunate clinical conundrum

Drug-resistant tuberculosis is an increasing healthcare challenge. Drug regimen building demands the use of different therapeutic groups, many of which harbor neurotoxicity as a side-effect, whether central or peripheral. Peripheral neuropathy is a major concern as it tends to be severe and usually irreversible. Anti-tubercular drugs that may contribute to peripheral neuropathy include INH, ethambutol, linezolid, cycloserine and para-amino salicylic acid. This potential adverse effect must be balanced against the intrinsically grave prognosis that drug resistant tuberculosis harbors. We present such a clinically challenging case of a 25 years-old female with extremely drug resistant tuberculosis whose treatment necessitated the use of several neurotoxic anti-tubercular drugs, leading to severe sensory peripheral neuropathy who did not improve despite the withdrawal of culprit drugs. She developed positive and negative sensory symptoms in both lower limbs. Nerve conduction studies were suggestive of sensory neuropathy affecting both lower limbs. Alternate causes of peripheral neuropathy including HIV, vasculitis, B12 deficiency and diabetes were ruled out. Despite drug withdrawal, the patient did not improve significantly. This case emphasizes the irreversibility of anti-tubercular therapy-induced peripheral neuropathy, demanding more rigorous clinical screening for the same while managing such patients.

Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Due to MTMR2 Mutations and Implications in Membrane Trafficking.

Charcot-Marie-Tooth type 4 (CMT4) is an autosomal recessive severe form of neuropathy with genetic heterogeneity. CMT4B1 is caused by mutations in the myotubularin-related 2 (MTMR2) gene and as a member of the myotubularin family, the MTMR2 protein is crucial for the modulation of membrane trafficking. To enable future clinical trials, we performed a detailed review of the published cases with MTMR2 mutations and describe four novel cases identified through whole-exome sequencing (WES). The four unrelated families harbor novel homozygous mutations in MTMR2 (NM_016156, Family 1: c.1490dupC; p.Phe498IlefsTer2; Family 2: c.1479+1G>A; Family 3: c.1090C>T; p.Arg364Ter; Family 4: c.883C>T; p.Arg295Ter) and present with CMT4B1-related severe early-onset motor and sensory neuropathy, generalized muscle atrophy, facial and bulbar weakness, and pes cavus deformity. The clinical description of the new mutations reported here overlap with previously reported CMT4B1 phenotypes caused by mutations in the phosphatase domain of MTMR2, suggesting that nonsense MTMR2 mutations, which are predicted to result in loss or disruption of the phosphatase domain, are associated with a severe phenotype and loss of independent ambulation by the early twenties. Whereas the few reported missense mutations and also those truncating mutations occurring at the C-terminus after the phosphatase domain cause a rather mild phenotype and patients were still ambulatory above the age 30 years. Charcot-Marie-Tooth neuropathy and Centronuclear Myopathy causing mutations have been shown to occur in proteins involved in membrane remodeling and trafficking pathway mediated by phosphoinositides. Earlier studies have showing the rescue of MTM1 myopathy by MTMR2 overexpression, emphasize the importance of maintaining the phosphoinositides equilibrium and highlight a potential compensatory mechanism amongst members of this pathway. This proved that the regulation of expression of these proteins involved in the membrane remodeling pathway may compensate each other's loss- or gain-of-function mutations by restoring the phosphoinositides equilibrium. This provides a potential therapeutic strategy for neuromuscular diseases resulting from mutations in the membrane remodeling pathway.

Pain and small-fiber affection in hereditary neuropathy with liability to pressure palsies (HNPP).

Background and aims Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal - dominant hereditary neuropathy caused by a deficiency in the peripheral protein PMP-22, due to deletion on chromosome 17p11,2 or in some rare cases point mutations in the PMP-22 gene. The clinical picture is characterized by recurrent mononeuropathies in nerves which frequently may be exposed to pressure, such as the median, ulnar, radial and peroneal nerves or also a more general neuropathy. Although pain is reported to be an unusual clinical symptom, there have been reports of pain in a surprisingly high proportion of these patients. Since pain may be explained by mechanisms in afferent small unmyelinated C- nerve fibers, an assessment of the function of small nerve fibers has been requested. The purpose of the present study was to investigate the presence of pain and the possible affection of afferent small nerve-fibers, A-δ and C-fibers, by quantitative sensory testing (QST)-assessment of thermal thresholds, as well as quantitative sudomotor axon reflex (QSART), a quantitative, validated assessment of efferent postganglionic sumodotor function. QST values were compared to values of age- and sex matched healthy subjects. Methods The 19 patients were investigated clinically, with an emphasis on pain characteristics, with nerve conduction studies (NCS) of major nerves in upper- and lower extremity, small fiber testing (QST, measurement of thermal thresholds) and with QSART. Results A total of 10 patients reported numbness in some extremity, suggesting entrapment of individual nerves as well as a general neuropathy, as verified by NCS in nine patients. A total of 15 patients had findings compatible with a general polyneuropathy. A total of eight patients reported pain, seven patients with pain in the feet, described as burning, aching, shooting and six with severe pathological QST values, mainly cold detection, but also four patients with elevated thresholds to warmth. Four of the patients had signs of a severe sensory neuropathy on NCS, with no sural findings. One patient had only pain in the arms, with only minor changes on NCS and with normal QST-values. Cold detection thresholds (CD) were significantly elevated (reduced sensibility) on the dorsum of the foot (mean of two feet), in patients [26.0 °C (19.7-28.0)] as compared with healthy subjects [28.6 °C (27.4-29.6) p = 0.000]. There were also significantly elevated warmth detection thresholds (WD) in feet in patients 39.5 °C (36.4-42.9) compared to healthy subjects [37.7 °C (36.1-39.4) p = 0.048]. However, there were no significant differences in QST values between patients with and without pain. Conclusions Of a total of 19 patients with verified HNPP, eight patients (42.1%) suffered from neuropathic pain, mainly in both feet. Implications Due to the high percentage of pain in HNPP, it is important not to disregard this diagnosis in a patient presenting with pain. Since there are no significant differences in QST values in patients with and without pain, routine QST studies in HNPP do not seem necessary.

Severe Guillain-Barr\xe9 syndrome associated with chronic active hepatitis C and mixed cryoglobulinemia: a case report

BackgroundWe describe a case of severe Guillain-Barre syndrome (GBS) associated with chronic active hepatitis C and mixed cryoglobulinemia (MC). To our knowledge, this association between GBS and hepatitis C virus (HCV) infection has been rarely reported.Case presentationA 56-year-old man developed symmetrical muscle weakness in all extremities, areflexia and sensorial disorder followed by acute respiratory failure associated with chronic active hepatitis C, which was confirmed by the presence of anti-HCV antibodies in the serum and persistence of HCV RNA viral load for more than 6 months. Chronic hepatitis C was further complicated by type 3 MC. Electromyography showed peripheral nerve injury (mainly in axon). A severe acute motor sensory axonal neuropathy (AMSAN) was diagnosed. After treatment with intravenous immunoglobulin and plasma exchange followed by antiviral therapy by direct-acting antiviral agent, patient showed progressive recovery and was transferred 3 months after his first admission to a rehabilitation center.ConclusionsOur case reported a severe GBS associated with HCV infection and MC. EMG classified for the first time the subtype of GBS (severe AMSAN) correlated with severe clinical form. HCV infection should be screened in high-risk patients to prevent silent progression of the chronic hepatitis C and its potentially severe extra-hepatic manifestations.

A rare case report on guillain barre syndrome and rheumatoid arthritis

A rare case report on guillain barre syndrome and rheumatoid arthritis - IJPCA- Print ISSN No: - 2394-2789 Online ISSN No:- 2394-2797 Article DOI No:- 10.18231/j.ijpca.2019.005, International Journal of Pharmaceutical Chemistry and Analysis-Int J Pharm Chem Anal

Patient-tailored FOLFIRINOX as first line treatment of patients with advanced pancreatic adenocarcinoma.

FOLFIRINOX is one of the most effective reference regimens in the 1st line treatment of locally advanced (LA) and metastatic pancreatic cancer (mPC), despite its high toxicity. We evaluated our real-life experience with “patient-tailored intent to treat FOLFIRINOX” in patients with LA or mPC compared to other reports along with the pivotal phase III trial.We analyzed data from all consecutive patients with pancreatic ductal adenocarcinoma treated with dose-modified FOLFIRINOX in 2016 at Paul Brousse University Hospital. Irinotecan was administered whenever initial serum bilirubin was <1.5 × upper limit of normal. Oxaliplatin was stopped for severe sensory neuropathy. Initial dose reductions were made according to patient profile (eg, age, comorbidities) and later due to toxicity. The treatment was continued until surgery or disease progression. Endpoints were time to progression (TTP), overall survival (OS), objective response rate (ORR), and secondary complete resection (R0R1).Thirty-seven patients with unresectable LA or mPC received patient-tailored FOLFIRINOX as 1st line chemotherapy. There were 22 male (59%) and 15 female patients (41%) aged 44 to 81 years with LA (18 patients, 49%) and mPC (19 patients, 51%). They had World Health Organization-performance status of 0 (59%) or 1 (41%). A total of 384 cycles were administered. Median dose intensities (mg/m2/w) were 28.9 for oxaliplatin, 56.8 for irinotecan, and 886.2 for 5-fluorouracil. Thirty-four patients were assessed for response; ORR and disease control rates were 47% and 85%, respectively. R0R1 rate was 30%. Median TTP and OS were 9.6 and 14.6 months. LA disease was associated with significantly longer TTP and OS (P < .001).FOLFIRINOX with patient-tailored dose adaptations seems to offer better results in patients with advanced PC. This approach in the neoadjuvant setting results in a macroscopic R0R1 in 61% of patients with initially unresectable disease. It deserves prospective evaluation to further improve outcomes in the management of advanced PC.