Acral Paresthesia Research Articles

Assessment of small fiber neuropathy in patients carrying the non-classical Fabry variant p.D313Y.

The pathophysiological significance of the Fabry-related, non-classical variant p.D313Y still remains to be solved. This study assesses the involvement of the peripheral nervous system with respect to small fiber neuropathy and neuropathic pain in female patients carrying p.D313Y. This study examined nine females carrying the Fabry-related p.D313Y variant by obtaining skin punch biopsies above the right lateral malleolus. Intraepidermal nerve fiber density was determined for each patient and compared to reference values matched for the patient's decade of life and sex. Moreover, each patient was characterized by a detailed neurological examination and by pain assessment via questionnaire. Compared to sex-matched lower fifth percentile reference values per decade, intraepidermal nerve fiber density was decreased in seven out of nine patients. Four patients reported acral paresthesias and neuropathic pain with an average visual analogue scale score of 7 out of 10 points. Two patients experienced acute pain crises. Six out of seven patients diagnosed with small fiber neuropathy had a their medical history of hypo- and/or hyperhidrosis. The diagnosis of small fiber neuropathy was made in seven out of nine females carrying the non-classical variant p.D313Y. Moreover, neuropathic pain and symptoms indicative of autonomic nervous system dysfunction seem to be common findings that may be of clinical significance and may warrant therapeutic intervention.

Fabry's disease manifesting as familial angiokeratoma corporis diffusum in an indian family – A rare occurrence!

Fabry's disease is a rare X-linked dermatosis, resulting from alpha-galactosidase deficiency and presents with both cutaneous (angiokeratoma, acral paresthesia, and hypohidrosis) and extracutaneous manifestations (ocular, cardiac, renal, and neurological). We report two brothers age 16 and 14 years that presented with multiple angiokeratoma in a bathing suit distribution on the trunk and the scrotum. The younger brother had acral paresthesia too. On systemic screening, ocular involvement was noted in both. Alpha-galactosidase assay in both brothers, revealed a deficiency of 19.2 nmol/h/mg (reference value

Patients with Sensory Symptoms of Acral Paresthesia: Routine Laboratory Findings in Neuromuscular Consultation

Patients with Sensory Symptoms of Acral Paresthesia: Routine Laboratory Findings in Neuromuscular Consultation

Incidence and Risk Factors for Post-thyroidectomy Hypocalcemia

Objectives. This study aimed to determine the incidence and risk factors for post-thyroidectomy hypocalcemia. Methodology. This was a retrospective study of 242 patients who underwent total or completion thyroidectomy from 2011-2014 at the St. Luke’s Medical Center, Quezon City, Philippines. The overall and type-specific incidences of hypocalcemia were determined. Patient and surgery-related factors were assessed and hypocalcemic events described. Results. Overall incidence of hypocalcemia is 11.98% distributed into symptomatic (10.74%) and asymptomatic (1.24%). The following patient-related factors were not found to be significantly associated with hypocalcemia: age, gender, thyroid disease and thyroid gland weight. Among surgery-related factors, the presence of concomitant complications of thyroidectomy (hoarseness and/or hematoma) and inadvertent parathyroidectomy were significantly associated with hypocalcemia both in the univariate [p=0.046; OR 2.369 (95%CI: 0.995-5.643) and p=0.027; OR 2.426 (95%CI: 1.084-5.432), respectively] and multivariate analyses [p=0.025; OR 2.842 (95%CI: 1.142-7.069) and p=0.013; OR 2.941 (95%CI: 1.252-6.907), respectively]. Other surgery-related factors were not found to be significantly associated with hypocalcemia: extent of thyroidectomy [total vs completion]; neck dissection; surgery duration (hours); and surgeon [consultant vs. trainee]. Among those with symptomatic hypocalcemia, manifestations occurred 29.85±23.07 hours post-operatively and these were: Chvostek’s (80.8%), acral paresthesia (76.9%), perioral numbness (46.1%), carpopedal spasm (15.3%), Trousseau’s (7.7%) and cramps (3.8%). Those who presented with manifestations of hypocalcemia but with normal serum iCa post-operatively comprised 33.9% of the study population and the majority presented with Chvostek’s sign (52%) and acral paresthesia (50%). Conclusion. In this study, hoarseness and/or hematoma and inadvertent parathyroidectomy are risk factors for post-thyroidectomy hypocalcemia. Closer monitoring of these patients for hypocalcemia may be necessary.

Parathyroid gland injuries during total and subtotal thyroidectomy

Objective The aim of this study was to identify the incidence, risk factors and the clinical relevance of incidental parathyroid excision during total and subtotal thyroidectomy in thyroid diseases. Background Postoperative hypocalcaemia is observed in total thyroidectomy patients and it is the most common complication. It is usually transient, and the incidence of permanent hyperparathyroidism is 3% or less. Despite being self-limiting in most patients, symptomatic hypocalcaemia is of particular concern because of a delay in its manifestation and the consequent need for prolonged patient hospitalization or readmission. Patients and methods In this randomized prospective study, we surveyed 30 patients who were admitted in the General Surgery Department, Menoufia University Hospital, during the period from November 2012 to March 2014 with benign thyroid diseases such as simple multinodular goiter, secondary toxic goiter, diffuse toxic goiter relapsing after full medical treatment, selected cases of thyroiditis (Hashimoto's thyroiditis) and thyroid cancer. Results We found two cases with temporary hypocalcaemia with multinodular goiter and medullary carcinoma. The typical signs and symptoms associated with hypocalcaemia are neuromuscular irritability, including perioral or acral paresthesia, muscle cramps that may progress to carpopedal spasm, laryngospasm, bronchospasm or even tetany. Treatment is based on the severity of symptoms. In severe cases (calcium levels less than 7.5% or severe symptoms), intravenous calcium salts are administered using one ampoule of calcium gluconate in 1 l of 5% dextrose at an initial infusion rate of 100 ml/h. With frequent monitoring of the serum calcium level (usually every 1-2 h), the infusion rate is titrated to keep the serum calcium level in the low normal range. Conclusion Incidental parathyroid excision during thyroid resection is not uncommon, and it occurred in 16.4% of the cases in this series. Total thyroidectomy, extra thyroid extension of the tumour, and thyroiditis were found to be the risk factors for incidental parathyroid excision.

Atypical Guillain–Barre sydrome presenting with isolated facial palsy and acral paresthesia

Bilateral simultaneous facial paralysis is a rare clinical entity, which unlike the unilateral presentation, is seldom secondary to Bell's palsy. A 26year-old-man presented with a one week history of bilateral facial weakness and acral paresthesia. Neurologic examination revealed bilateral complete lower motor neuron type of facial palsy, loss of deep tendon reflexes and diminished vibratory sensation. But motor examination was completely normal in both upper and lower extremities. Blood tests for full blood counts, urea and electrolytes, serum angiotensin converting enzyme (ACE) and the vasculitic screen were within normal limits.

An Uncommon Presentation of Adult Hemophagocytic Lymphohistiocytosis with Severe Pulmonary Hypertension

Abstract 4734 Introduction:Adult hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening hyperinflammatory syndrome that presents both diagnostic and therapeutic challenges. HLH may be primary and related to an underlying genetic abnormality or secondary to infection, malignancy, or rheumatologic condition. We describe a case of HLH in a latently EBV-/CMV-/HBV-immune 52-year old male co-presenting with severe pulmonary hypertension and a novel heterozygous perforin missense exon mutation. He was intolerant of the HLH 2004 protocol but responded to salvage alemtuzumab therapy, which was then followed seven weeks later by a fatal polymicrobial sepsis. Case Presentation:This previously healthy 52 year-old male developed the insidious onset of acral paresthesia and exertional dsypnea over a two year period. Seven months prior to admission, he was treated as an outpatient for suspected H1N1 infection, followed by the development of spontaneously-resolving superior oblique nerve palsy, with the EMG/NCS correlate of demyelinating polyneuropathy and secondary axonal loss. His dyspnea progressed, and he presented to hospital with fevers, weight loss, and respiratory distress requiring mechanical ventilation. His course in the intensive care unit was complicated by nephrotic range azotemia (Cr >200 umol/L), cryptogenic hepatitis (transaminases >1000 IU/ml), and splenomegaly. Hematologic investigations initially revealed an isolated thrombocytopenia that was IVIg and steroid refractory, followed by hemolytic anemia with oxidative blood film abnormalities, and an initial bone marrow biopsy devoid of hemophagocytosis. Rheumatologic serologies (ANA, ENA, C3, C4, p-ANCA, c-ANCA, ds-DNA, anti-GBM) and microbiologic studies (HIV, Monospot, and indices of reactivation of HBV or CMV) were negative. Other causes of peripherally destructive cytopenias were also ruled out (DAT, PNH flow cytometry, APLA, ADAMTS13, methemoglobin, G6PD, PK normal).Four weeks after admission, worsening pancytopenia and unexplained fevers prompted a second bone marrow examination, which demonstrated hemophagocytosis with an EBV reactivation viral load of 7 × 105/ml. Meeting clinicopathologic diagnostic criteria for HLH, the HLH 2004 protocol was thus initiated. Within 7 days, treatment-limiting nephrotoxicity and hepatotoxicity developed, prompting discontinuation of cyclosporine and dose-reduction of etoposide. Hepatic biopsy revealed drug-induced sinusoidal necrosis without lymphohistiocytic infiltration. Worsening HLH prompted the next-line use of anti-CD52 monoclonal therapy (alemtuzumab), which associated with the onset of freedom from transfusion within 35 days. Over the six week course of therapy, clinical, biochemical, and hematologic manifestations continued to improve. In parallel with sildenafil, the pulmonary hypertension was also dramatically alleviated. He thus remained in a transfusion-free remission for 55 days until day 105 after diagnosis.Fevers then recurred, with polymicrobial sepsis complicated by disseminated intravascular coagulation, respiratory failure, and hematopathologic evidence of macrophage re-activation. The goals of care were changed to comfort measures and the patient succumbed. Autopsy revealed disseminated blastomycosis with relapsed HLH. Perforin gene sequencing identified a novel heterozygous exon missense single nucleotide polymorphism 1517A>C (His506Pro). Conclusion:This is an extraordinary case of adult EBV-reactivation-associated HLH presenting with severe pulmonary hypertension, a novel perforin gene mutation, intolerance towards the HLH-2004 protocol, and responsiveness to alemtuzumab. Fatal secondary infections, including the discovery of disseminated blastomycosis, presaged or provoked the concomitant relapse of HLH. The relevance of the unique perforin mutation or the co-infection with Blastomyces with respect to the atypical features of this HLH presentation remains unknown. Disclosures:Off Label Use: Alemtuzumab (anti-CD52) was used off-label in the salvage management of hemophagocytic lymphohistiocytosis (HLH).

Clinical Reasoning: A 34-year-old woman with recurrent bouts of acral paresthesias

A 34-year-old, previously healthy woman presented with a 3-year history of persistent numbness and tingling in her feet ascending to the knees. She was a lifelong long-distance runner, and she normally experiences numbness and tingling in both feet while running that resolve within minutes of stopping her exercise. Three years ago, she developed diarrhea that was followed a week later by paresthesias in her feet and legs with a stocking distribution to the knees. Her symptoms were associated with a transient feeling of overwhelming fatigue, limiting her ambulation to 1 city block. She did not, however, have any functional weakness. After 2 weeks, milder hand and left face paresthesias developed. Four weeks later, her symptoms plateaued and persisted. Three months later, she developed more intense paresthesias and a sensation of “crawling” below both knees. At that time, she was seen at another hospital, where the examination showed bilateral pes cavus and hammertoes. There was no nerve thickening. Cranial nerves were intact. Strength was normal except for mild bilateral thenar weakness and slight difficulty with heel walking. The deep tendon reflexes were decreased at the arms and ankles. There was decreased pinprick sensation in the feet in a stocking-glove distribution with hyperalgesia. Vibration was moderately diminished at the ankles. Nerve conduction studies and electromyography (NCS/EMG) at that time showed uniform, mild conduction velocity slowing of both sensory and motor conduction with borderline prolonged distal latencies in the median and ulnar nerves. She was treated with a 1-month taper of prednisone beginning with 80 mg daily. The crawling sensation resolved and the paresthesias became less intense and stabilized. She was able to resume distance running, but still had persistent, mild numbness in her feet with bouts of increasing intensity every several months. Three years later, the patient presented to us for a …

Oxaliplatin-induced neuropathy in the rat: Involvement of oxalate in cold hyperalgesia but not mechanical allodynia

Oxaliplatin is a key drug in the treatment of advanced metastatic colorectal cancer, but it causes acute peripheral neuropathy (acral paresthesias triggered by exposure to cold) and chronic neuropathy (abnormal of sensory and motor dysfunction). Oxaliplatin is metabolized to oxalate and dichloro(1,2-diaminocyclohexane)platinum (Pt(dach)Cl2). Although the chelating of Ca2+ with oxalate eliminated from oxaliplatin is thought as one of the reasons for the neuropathy, there is little behavioral evidence. In this study, we investigated the involvement of oxalate in the oxaliplatin-induced peripheral neuropathy in rats. Oxaliplatin (4mg/kg, i.p., twice a week) induced cold hyperalgesia/allodynia (cold-plate and acetone tests) in the early phase, and mechanical allodynia (von Frey test) in the late phase. Oxalate (1.3mg/kg, i.p., twice a week) induced the cold hyperalgesia/allodynia in the early phase, but did not induce the mechanical allodynia. On the other hand, Pt(dach)Cl2 (3.8mg/kg, i.p., twice a week) induced the mechanical allodynia in the late phase, but did not induce the cold hyperalgesia/allodynia. The pre-administration of calcium or magnesium (0.5mmol/kg, i.v.) before oxaliplatin or oxalate prevented the cold hyperalgesia but not mechanical allodynia. However, the treatment with calcium or magnesium after the development of neuropathy could not attenuate the cold hyperalgesia or mechanical allodynia. These findings suggest the involvement of oxalate in oxaliplatin-induced cold hyperalgesia but not mechanical allodynia, and usefulness of prophylactic treatments with calcium and magnesium on the acute peripheral neuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with inflammatory bowel diseases: questioning the autoimmunity hypothesis

Dear Editor: Inflammatory bowel diseases (IBD) are chronic disorders encompassing Crohn’s disease (CD) and ulcerative colitis (UC) characterized by abnormal mucosal immune response. Early pathology coincides with intestinal, mesenteric T-cell infiltration, cytokine production, bowel inflammation, and vasculitis. There is evidence that CD4 and CD8 T-cells can trigger autoimmunity when peripherally activated by antigens in a proinflammatory setting. Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) are caused by immune responses mounted against uncharacterized epitopes. Polyneuropathies associated with IBD exhibit different phenotypes. We studied two patients with CIDP associated with IBD supporting the view of common causality. A 63-year-old woman experienced rectal hemorrhage, acral numbness, and unsteady gait during acute hepatitis. Intestinal biopsy diagnosed CD. Neurologic examination showed absent jerks and distal loss of all sensory modalities. Muscle strength was minimally affected. Normal laboratory results included B12, E vitamin serum level, tumor markers, microbial, and immunological screenings. Sural-evoked responses were either absent or diminished in amplitude with slowed velocity. There were prolonged F wave and distal latencies of median, tibial, and peroneal muscle action potentials. Sural biopsy showed fiber loss and demyelination in 30% of fibers teased. Onion bulbs and mononuclear inflammatory cells were absent. Patient was treated with long-term steroids. On clinical follow-up, her neurological disability progressed in the absence of CD recurrence. Sixteen years after onset, distal strength was graded 3/5, whereas ataxia was marked and distal sensation was severely impaired. Electrophysiology confirmed demyelination. The second patient when aged 33 was diagnosed having UC. Twelve months later, he developed acral paresthesias and extremity weakness graded 3/5 on examination. Deep jerks were unevokable; Romberg sign was positive, and touch and deep sensation was distally impaired. In nerve conduction, there were partial motor conduction block, abnormal temporal dispersion, and diminished velocity along median, ulnar, peroneal, and tibial nerves. Patient refused spinal tap. Treatment with metronidazole was not given. Repeated courses of intravenous immuneglobulins had benefit. Our patients presented common features of moderate distal rather than proximal weakness and ataxia due to proprioceptive sensory loss. Electrophysiology suggested in both ongoing multifocal demyelination, which was histologically proven in case 1. Neurological illness began acutely in patient 1 at CD onset, raising the question of a sensory variant of acute inflammatory demyelinating polyradiculoneuropathy or of CIDP with acute onset. UC of case 2 predated by 12 months his neuropathy, which improved with immunemodulating therapy and ultimately relapsed. Gondim et al. reported seven CIDP cases associated in three with CD and in four with UC: The three CD had more proximal than distal Int J Colorectal Dis (2009) 24:603–604 DOI 10.1007/s00384-009-0646-x

Crossed cheiro-oral syndrome

Objectives Cheiro-oral syndrome is characterized by sensory impairment confined to perioral area and ipsilateral fingers/hand. It results from an involvement of the ascending sensory tracts above the pons. However, a crossed pattern of perioral and acral paresthesia was rarely reported before. Patients and methods This study reports the neuroanatomic relationship, course and clinical significance of perioral and contralateral acral paresthesia in four patients. We term it the crossed cheiro-oral syndrome. Results All patients had lateral or dorsolateral medullary infarctions that were ipsilateral to their perioral paresthesia. The contributory origin is considered a diagonal lesion involving the par oralis fibers within the descending trigeminal sensory tract and acral portion of the lateral spinothalamic tract at the lateral portion of medulla oblongata. Despite of a restricted sensory disturbance at initial, progressive neurological disability terminated to Wallenberg's syndrome ensued in three patients and disabling deficits persisted in two of them. Conclusion The crossed cheiro-oral syndrome seems a mild form of Wallenberg's syndrome. Therefore, it predicts medullary involvement and is also a warning sign for progression.

Fabry disease: Case report with emphasis on enzyme replacement therapy and possible future therapeutic options

A 38-year-old male Caucasian with Fabry disease presented with angiokeratomas and tortuous conjunctival and retinal vessels. Additionally, the patient showed characteristic skin lesions of psoriasis and seborrheic dermatitis. His past medical history revealed anhidrosis, acral paresthesias, myocardial infarction, phlebothrombosis, hypertension, antithrombin III deficiency, factor V Leiden disease, chronic obstructive lung disease, tinnitus, diarrhea, recurrent abdominal pain, headache, and depressive mood. He was treated with intravenous substitution of the deficient enzyme alpha-galactosidase A. Possible future options in treatment of Fabry disease are discussed.

SENSORY‐MOTOR POLYNEUROPATHY IN A PATIENT WITH MITOCHONDRIAL MYOPATHY

Benedetti L.1, Grandis M.1, Bruno C.2, Bado M.2, Abruzzese M. 1, Mancardi G.L.1, Schenone A.1 1Department of Neurological Sciences and Vision, University of Genoa, 2Operative Unit of Neuromuscular Disease, Gaslini Hospital, University of GenoaMitochondrial myopathy is a multisystem disease with heterogeneous clinical manifestations. The existence of neuropathy has been described in mitochondrial disorders such as MELAS, MERRF, Leigh's syndrome, the Kearns‐Sayre syndrome and progressive external ophthalmoplegia and constitutes a basic component of the NARP (neuropathy, ataxia and retinosis pigmentosa). We describe a 36‐year‐old woman who came to our observation 12 years ago for external ophthalmoplegia and bilateral ptosis. Morphological examination of a muscle biopsy suggested a mitochondrial myopathy. Genetic studies ruled out the typical mitochondrial DNA‐mutations. One year ago she started to complain of acral paresthesias and gait imbalance. Neurological examination revealed, besides the signs of a myopathy, reduced tendon reflexes, distal sensory impairment and a positive Romberg sign. Nerve conduction studies showed mild slowing of motor conduction velocity on right and left peroneal nerves, with normal amplitude of cMAP, and mild to severe slowing of sensory conduction velocity on both sural nerves, with reduced amplitude of SAP. Therefore a predominantly sensory‐ataxic neuropathy was diagnosed.A polyneuropathy may be a common finding in mitochondrial disorders and is probably underdiagnosed. Since the onset of neuropathic symptoms and signs may follow the diagnosis of mitochondrial myopathy, nerve conduction velocity studies could be of help in disclosing subclinical cases.

Sexual dysfunction in nonseminoma testicular cancer patients is related to chemotherapy-induced angiopathy.

To establish the prevalence of sexual dysfunctions after different treatment modalities for nonseminomatous testicular germ cell tumor (NSTGCT) and to investigate whether treatment-induced angiopathy and neuropathy is related to sexual dysfunction. A questionnaire assessing sexual dysfunction was sent to 255 NSTGCT survivors. Polychemotherapy (PCT) regimens (cisplatin, vinblastine, and bleomycin [PVB], vinblastine substituted by etoposide [BEP], or cisplatin substituted by carboplatin [CEB], etoposide combined with cisplatin [EP], or with ifosfamide and cisplatin [VIP] were compared regarding treatment-induced angiopathy and neuropathy. Sexual dysfunctions were related to Raynaud's phenomenon and acral paresthesia. Among the 215 responders, 56 (26%) had been treated by orchidectomy and surveillance, 42 (19.6%) by PCT, and 117 (54.4%) by PCT and resection of residual retroperitoneal tumor mass (RRRTM). Overall, loss of libido was reported by 19.1%, decreased arousal by 11.2%, erectile dysfunction by 12.1%, decreased intensity of orgasm by 20%, and ejaculatory problems by 28%. Patients treated with PVB suffered more often from Raynaud's phenomenon compared with those treated with other regimens (40.4% v 29%; P < .05) and from paresthesia (31.6% v 14.7%; P < .05). Patients with Raynaud's phenomenon had more often erectile dysfunction (28.8%) compared with those without (8.4%) (P < .05). Compared with orchidectomy alone, PCT, with or without RRRTM, induced more often posttreatment sexual dysfunction. Compared with other chemotherapeutic regimens, signs of angiopathy and neuropathy were most prevalent in those treated with PVB. Erectile dysfunction was related to the chemotherapy-induced Raynaud's phenomenon but not to acral paresthesia.

Peripheral neuropathy and multiple myeloma in aging: A case report

A 67-year-old man affected by moderate weight loss, acral paresthesia and plantar burning sensation was admitted to our department. Electromyographic (EMG) and electroneurographic (ENG) studies confirmed a peripheral, asymmetrical, motor-sensorial polyneuropathy (PPN). Hematological data and bone marrow biopsy discovered a non-secerning multiple myeloma (MM). All other probable causes of peripheral neuropathy could be excluded, and the possible relationship between nerve damage and neoplasia was confirmed. Furthermore, all possibilities of association of MM with PPn, namely the osteosclerotic variant, the Crow-Fukase syndrome, and the amyloid one have been evaluated. The only finding of osteolytic bone areas by radiology, the absence of organomegaly, diabetes mellitus, skin alterations, and of amyloid deposition in muscles and nerves, exclude the possible connection of the case to any of the listed possibilities. On the other hand, some clinical aspects differ, in part, to others described in the literature. In conclusion, the association between PPN and MM as the result of multiform clinical variants could be considered.