Type: Evaluation Essays
Sample donated: Heather Cortez
Last updated: August 26, 2019
Titleof Article: A Mimic of Immune Mediated Neuropathy Corresponding Author: Dr SimonCronin, Department of Neurology, Cork University Hospital, Cork, Ireland. [email protected]
ieCo-author: Dr Eimear McAuliffe, Departmentof Neurology, Cork University Hospital, Cork, Ireland. Co-author: Dr Mary Clare McKenna, Departmentof Neurology, Cork University Hospital, Cork, Ireland Word Count: 1,296 Abstract:A54-year-old male presented with a 2 year history of progressive distal weaknesswith numbness. He has a background of type 2 diabetes mellitus, hypertensionand a history of alcohol excess. His initial examination demonstrated weaknessand sensory loss distally.
His symptoms progressed rapidly over six months.Following investigation, he was commenced on a trial of intravenousimmunoglobulin (IVIg) which resulted in clinical improvement. A diagnosis ofdistal axonal chronic inflammatory demyelinating polyneuropathy was made. It isimportant to evaluate clinical symptoms and signs, to recognise patterns ofperipheral neuropathy and thus arrive at a diagnosis. Adifficult caseAMimic of Immune Mediated Neuropathy EimearMcAuliffe1, Mary Clare McKenna1, Simon Cronin11.Departmentof Neurology, Cork University Hospital Case ReportA54-year-old right handed male presented with a 2-year history of progressivepainful tingling in his hands and feet. The hands were more affected than the feet, and symptoms were moreprominent on the left. He was unable to do buttons or tie shoelaces over theprevious year.
He complained of reduced grip strength. His motor symptoms wereongoing 1 year. He felt as if he was “standing on nails”. He complained ofswollen feet in the mornings. He was diagnosed with type 2 diabetes mellitus 1year ago and was treated with oral hypoglycaemic agents. He had a background ofhypertension, elevated body mass index and a history of alcohol excess. Hissister had died of motor neuron disease at age 62 with disease onset age 58.
There was no history of recent infection.Onexamination, he had a broad-based gait. Cranial nerves were intact. Neckflexion and extension were 5/5.
Bilaterally, shoulder abduction was 4++/5,wrist extension 4+/5 bilaterally, opponens pollicis and abductor digiti minimi3+/5 bilaterally. Pin prick and temperature were reduced distally to midforearm. Joint position sense and vibration were preserved in the upper limbs.
Deep tendon jerks were normal in the upper limb. There was pseudoathetosis andimpaired coordination in the upper limb with eyes closed. There was dysmetria in the upper and lowerextremities. Hip and knee power was 5/5. There was bilateral mild ankle dorsiflexionweakness 4+/5. Pin prick and temperature were reduced distally to knees.
Jointposition sense was preserved in the lower limb. Vibration was reduced to thetibial tuberosity bilaterally. There were no fasciculations. Deep tendon jerkswere absent.
Plantars were downgoing. Allodynia was noted. He was soft Rhombergpositive.
Peripheralneuropathy blood screening tests demonstrated an elevated glycated haemoglobin(HbA1c) 63 mmol/mol (20-42 mmol/mol). Fasting lipids including totalcholesterol (6.6 mmol/L, (3.5 – 5 mmol/L) and triglycerides (3.9 mmol/L, (0.3 –1.7 mmol/L) were elevated.
Additional blood tests included normal urea andelectrolytes, thyroid function tests, haematinics, erythrocyte sedimentationrate and serum protein electrophoresis. HIV, Hepatitis B and Hepatitis C,syphilis and Lyme serology were all negative. Rheumatoid factor, antinuclearand anti-neutrophil cytoplasmic were negative. Theinitial clinical diagnosis was moderately severe diabetic axonal motor andsensory neuropathy. Despite improving glycaemic control by reducing HbA1c to58mmol/mol (20-42mmol/mol), his symptoms progressed over the next 6 months. Hehad increasingly painful tingling in his hands and feet. Numbness now extendedto his mid thighs.
Sensory symptoms were again more pronounced on the left. Hishands and feet felt weaker. His pain was worse.
Clinically, he now had wastingof the intrinsic muscles of the hands. Opponens pollicis and abductor digitiminimi 3/5 bilaterally. Fasciculations remained absent.
Pin prick andtemperature were reduced distally to upper arms. Joint position sense andvibration remained preserved in the upper limbs. He was distally weak withankle and hallux dorsiflexion 3+/5. Vibration remained reduced to the tibialtuberosity bilaterally.
Joint positionsense was now impaired in the feet. He was Rhomberg positive.Nerveconduction studies and electromyography (NCS/EMG) showed absent sensoryresponses throughout and reduced motor amplitudes with reduced conductionvelocity. Giventhe rapid progression of his symptoms, the initial diagnosis of diabetic axonalneuropathy was re-evaluated. The differential based on clinical and NCS/EMGfindings included severe diabetic neuropathy, chronic inflammatorydemyelinating polyneuropathy (CIDP) or a late presentation of an inheritedneuropathy. He was referred for sural nerve biopsy which excluded vasculitisand amyloidosis; it could not differentiate between diabetic neuropathy, CIDPor an inherited neuropathy (such as a connexin 32 mutation). Magnetic resonanceimaging (MRI) of the cervical spine showed no focal signal abnormality orsyrinx in the cervical cord, bilateral foraminal stenosis at C3-C4, and rightforaminal stenosis at C5-C6 with possible impingement of the exiting nerveroots.
There was no gadolinium enhancement of the nerve roots. Cerebrospinalfluid analysis demonstrated protein 622mg/L which was high (200-400 mg/L).Anti-myelin associated glycoprotein (anti-MAG) and antiganglioside 1 (GM1)antibodies were negative.
Connexin 32 genetic screening excluded pointmutations, making a diagnosis of axonal Charcot Marie Tooth unlikely. A 5-daytrial of intravenous immunoglobulin (IVIg) was given (2g/kg split over 3 days).On the 4th day hand dexterity improved significantly; the patient was now ableto fasten buttons. Bilateral shoulder abduction was 5/5, wrist extension was5/5, opponens pollicis and abductor digiti minimi 3+/5.
Themaximum effect was sustained for 10 days and he then returned to an improvedbaseline. A diagnosis of reversible, immune mediated neuropathy responsive toIVIg was made. Possible diagnoses included an atypical upper limb predominantCIDP phenotype or multi-focal motor neuropathy with conduction blocksuperimposed upon diabetic neuropathy. The patient was further treated with2g/kg of IVIg over 3 consecutive days given monthly for 3 months, then every 6weeks. He remains clinically stable at an improved baseline and is independentin his activities of daily living.
He mobilises independent of a frame orstick. He attends for infusions of IVIg every 6 weeks. DiscussionTheaetiology of peripheral neuropathy may be difficult to ascertain. It may beinherited or acquired. Diagnosis is based on history, clinical examination,laboratory investigations, and neurophysiology. Electrodiagnostic tests help todifferentiate conditions that affect the nerve axon (axonopathies) or themyelin sheath (myelinopathies)1.
In a review of 205 patients withundiagnosed peripheral neuropathy referred to the Mayo Clinic, a diagnosis wasmade in 76% of patients1. A hereditary cause was found in 42%,inflammatory neuropathy such as CIDP in 21%, and the remaining 13% were due toother diseases such as diabetes, malignancy and vitamin deficiencies. ChronicInflammatory Demyelinating Polyneuropathy is an inherited condition which ischaracterised by slow onset of sensorimotor symptoms which are generallysymmetrical. There is not just one phenotype and it has been suggested thatCIDP is part of a spectrum of similar conditions. Due to the variation inclinical presentation identification of the disease can be difficult. In thiscase, a diagnosis of CIDP is supported by a history of gradual onset ofproximal and distal weakness in the upper and lower extremities, with a raisedCSF protein, electrodiagnostic findings, and clinical response to IVIG.
Theasymmetry is a little atypical suggesting additional inflammatory nerve rootinvolvement however there was no enhancement of nerve roots on gadolinium MRI.Anti ganglioside 1 antibodies were negative however this can often be the case.There is now evidence that CIDP can be due to antibodies directed at Schwanncells or nodal antigens and not just against myelin2. It is nowthought that nodal antibodies can be present in 30% of patients with CIDP2. Themain differential diagnosis was an acquired diabetic sensorimotorpolyneuropathy causing demyelination due to poor glycaemic control however thiswould be expected to present with symmetric distal sensory loss, with orwithout distal weakness. Autonomic dysfunction may also feature.
Symptomsworsened despite improving glycaemic control. Simultaneous presence of diabetesmellitus type 2 (DM2) and CIDP has been seen in clinical practice however it isunknown if they are genetically linked. Some studies have suggested anincreased risk of CIDP in patients with DM2. There is also the dilemma of howto treat CIDP in patients with diabetes mellitus as systemic steroids are knownprecipitants of insulin resistance therefore treating with immunoglobulin isoften more sensible.
Helpfulclues in making the diagnosis include defining the anatomy, clarifying thedistribution of weakness, the extent of sensory involvement, the presence orabsence of upper motor neuron involvement, the temporal evolution and familyhistory if known. This case highlights the importance of the clinical patternand temporal evolution of peripheral neuropathy in making a diagnosis. It showshow diagnosis is often not clear at presentation and clinicians shouldsystematically examine the history, clinical exam, laboratory investigations,and neurophysiology before choosing the most suitable treatment regimen for thepatient in question. KeyPoints1. The importance of the clinical patternin making a diagnosis of peripheral neuropathy2. The importance of correlation ofclinical evaluation and electrodiagnostic findings3.
Symptom response to treatment can helpwith diagnosis. 4. The emerging role of autoimmuneantibodies in the diagnosis of peripheral neuropathy References1.
Barohn, R. and Amato, A. (2013).Pattern-Recognition Approach to Neuropathy and Neuronopathy. NeurologicClinics, 31(2), pp.343-361.2. Mathey EK, Park SB, Hughes RAC, et al.
Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology tophenotype. Journal of Neurology, Neurosurgery, and Psychiatry.2015;86(9):973-985. doi:10.