Yusuf A. Rajabally

Optimizing the use of electrophysiology in the diagnosis of chronic inflammatory demyelinating polyneuropathy: a study of 20 cases.

Abstractu2003 Current electrophysiologic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) are highly specific but poorly sensitive. The required extensiveness and best practical way of performing nerve conduction studies to achieve optimal sensitivity remain unknown. We here initially retrospectively analyzed the motor nerve conduction study results of 20 consecutive patients with a clinical diagnosis of CIDP (four performed prior to, and 16 after, treatment initiation) to assess the sensitivity of six published sets of criteria (Nicolas et al., 2002; Thaisetthawatkul et al., 2002; Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce, 1991; Magda et al., 2003; Hughes et al., 2001; Saperstein et al., 2001), as well as four combinations (Nicolas et al., 2002; Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce, 1991; Hughes et al., 2001; Saperstein et al., 2001, each individually combined with Thaisetthawatkul et al., 2002). Sensitivity was highest for the combination of Nicolas et al. (2002) and Thaisetthawatkul et al. (2002) (100%). We then determined the sensitivity of this combined criteria, using five different, hypothetical, nerve conduction study protocols, applied retrospectively to the neurophysiologic data of our 20 patients (exclusive upper limb studies with proximal stimulations; exclusive lower limb studies; full forearm and foreleg studies without proximal stimulations; right‐sided studies with proximal stimulations; and left‐sided studies with proximal stimulations). The findings showed that exhaustive upper limb or, alternatively, four‐limb forearm and foreleg testing would have proved considerably more sensitive than unilateral or lower limb studies to achieve an electrophysiologic diagnosis of CIDP.

Dose of intravenous immunoglobulins in chronic inflammatory demyelinating polyneuropathy

Abstractu2003 The usual initiating dose of intravenous immunoglobulins (IVIg) in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) is 2 g/kg/course. Although not evidence based, subsequent reductions are advised to the lowest possible level for maintenance. In practice, the achievable levels of such reductions and their impact on treatment frequency have not been studied. Factors determining maximal dosage reduction are unknown. We retrospectively reviewed data concerning IVIg therapy for 15 patients with CIDP, from their medical records between 1997 and 2005. Lowest effective dose and treatment frequency were determined. The following correlations were ascertained: dose to frequency, dose to weight, dose to disease duration, amplitude of dose reduction to disease duration, and dose to pre‐therapeutic disease severity. Dose reductions were possible in all (mean: 63.3%, range: 42.4–88%). The lowest effective dose of IVIg per course and treatment frequency were both very variable (18–108 g and 2–17 weeks, respectively). Lowest dose per course did not correlate to weight, frequency of administration, disease duration, or pre‐therapeutic degree of disability. Amplitude of dose reduction achieved was independent of disease duration. Treatment frequency could not be lowered in any patient. Our findings show that IVIg target doses should be titrated individually but suggest that infusion frequencies are fixed in each case in relapsing CIDP. Importantly, lower dose treatment is not associated with shorter intervals between courses, and lowest effective dose is independent of weight and disease duration. Initial level of disability does not appear to influence dose required. These results suggest considerably lower, standardized, initiating, and maintenance doses might be effective and highlight the need for prospective dose comparative trials.

Proximal nerve conduction studies in chronic inflammatory demyelinating polyneuropathy

OBJECTIVEnThe purpose of this study was to evaluate the sensitivity and specificity of proximal upper limb motor nerve conduction study abnormalities in chronic inflammatory demyelinating polyneuropathy (CIDP), using standard percutaneous stimulations up to Erbs point.nnnMETHODSnElectrophysiologic data relating to proximal conductions of median and ulnar nerves of 22 patients with CIDP were retrospectively analyzed and compared to those of 22 controls with sensory neuropathy. Distal conduction results were also reviewed.nnnRESULTSnThe findings demonstrate independent high sensitivity of abnormal upper limb proximal nerve conduction studies in CIDP. Demonstration of conduction block of >20% and temporal dispersion of >15% had low specificity. However, conduction block was highly specific with cut-off values of >30% at axilla and >50% at Erbs point. Specificity was considerably improved using a cut-off value of >30% at proximal levels for temporal dispersion. Diagnostic sensitivity improved significantly with proximal studies with the criteria used in this population. No adverse effects had occurred as result of proximal stimulations.nnnCONCLUSIONSnProximal studies are safe, sensitive and reliable procedures in cases of suspected CIDP. Their use appears justified although adequate cut-off values are desirable to optimize their specificity.nnnSIGNIFICANCEnThis study indicates that proximal upper limb nerve conductions are appropriate in investigating suspected CIDP, as detailed in recently established electrophysiologic criteria. However, specificity is largely dependent on cut-off values for conduction block and temporal dispersion.

Clinical heterogeneity in mild chronic inflammatory demyelinating polyneuropathy.

We describe the clinical presentation, progression and electrodiagnostic features of three patients with a mild form of chronic inflammatory demyelinating polyneuropathy (CIDP). The unusually mild but also variable clinical picture was a cause of diagnostic uncertainty in all, but CIDP was eventually confirmed by extensive electrophysiological studies in each case, as well as by histology in one. Cerebrospinal fluid protein was raised in only one patient. Two patients were treated by intravenous immunoglobulins and both improved. Awareness of the existence of this relatively benign form of CIDP in its various presentations is essential as it can be functionally disabling, progress to more severe symptomatology, and as patients may benefit from immunomodulatory therapy.

Value of distal compound muscle action potential duration prolongation in acute inflammatory demyelinating polyneuropathy: A European perspective

Introduction: The value of distal compound muscle action potential duration (DCMAPD) has not been widely studied in acute inflammatory demyelinating polyneuropathy (AIDP) with electromyography (EMG) equipment at low‐cut filter settings <10 Hz, as used in Europe. Methods: We retrospectively reviewed the records of 40 patients with AIDP and 40 controls with axonal neuropathy, from Leicester, UK, and Angers, France. Results: The best combination of sensitivity/specificity for AIDP using DCMAPD prolongation in any one nerve was offered by cut‐offs from two other studies (sensitivity: 90% and 87.5%, respectively; specificity: 92.5% for both). Independent DCMAPD prolongation in any one nerve was better than, or equivalent to, other criteria. Conclusions: DCMAPD prolongation in any one nerve, at cut‐offs suggested by prior studies, represents a sensitive and specific marker to aid/simplify electrodiagnosis of AIDP in patients studied with EMG equipment with low‐cut filter settings of <10 Hz. Muscle Nerve, 2011

Charcot-Marie-Tooth disease due to the Thr124Met mutation in the myelin protein zero gene associated with multiple sclerosis.

Dear Editor, Charcot-Marie-Tooth (CMT) disease has only rarely been reported in association with multiple sclerosis (MS) (Almsaddi et al., 1998; Frasson et al., 2004). Here, we report such an association in a case of CMT because of a Thr124Met mutation in the myelin protein zero (MPZ) gene. This patient’s presenting symptoms at the age of 49 years consisted of distal paresthesias in the lower limbs. She then experienced fasciculations in the distal muscles, as well as a gradual bilateral, predominantly right-sided foot drop. The motor weakness progressed very slowly also gradually involving the proximal lower limb muscles but sparing the arms. Prior to the recent events, she could walk with the help of one stick. Her past history consisted of thyrotoxicosis, vitamin B12 deficiency, both treated effectively, and of chronic lymphatic leukemia, for which she had not received any treatments. She had a family history of neuropathy, having affected her father in his mid-50s, her brother as well as a first-degree cousin on the paternal side (paternal uncle’s daughter) in their early 30s. Her daughter, in her 30s, as well as her grandson (aged 5 years), who had never complained of neuropathic symptoms, had both been seen in the ophthalmology unit for irregular, unreactive pupils. Diagnosed with CMT type 2 in the late 1990s following nerve conduction studies which had shown normal motor conduction velocities (detailed results were unavailable), she was referred back to our department in November 2003, then aged 58, for rapid recent deterioration in her neurological state, describing increased leg weakness, left arm heaviness, and painful dysaesthesiae affecting the trunk. On examination at this stage, tone was found to be normal in the legs, but slightly increased in the left arm. Pes planus with moderate peroneal atrophy was present. Power was reduced in a symmetrical pattern in the lower limbs of grade 3 proximally and grade 2 distally on the Medical Research Council scale. Patellar reflexes were present and brisk, Achilles reflexes were absent and plantar responses flexor. Left upper limb power was reduced of grade 4 proximally and of grade 3 distally. Reflexes were all present, normal and equal in the upper limbs. Sensory loss to all modalities was detected in the distal lower limbs with, in addition, a sensory level at T8–T9. Examination of the cranial nerves showed pupils in the intermediate position, totally unresponsive to light and accommodation. The patient complained of mild hearing problems that had appeared slowly over years. No obvious clinical hearing impairment was, however, detected, Rinne’s test being positive bilaterally. Nerve conduction studies showed an axonal sensorimotor polyneuropathy with a moderately slowed conduction velocity for the left median nerve at 37 m/s. A magnetic resonance imaging (MRI) brain scan showed periventricular and pericallosal white matter hyperintensities on T2 and FLAIR sequences suggestive of demyelination. A spinal MRI revealed similar lesions at the level of the cervico-medullary junction and in the cord between C2 and C4. Cerebrospinal fluid examination showed no oligoclonal bands. Creatine kinase was normal. An audiogram showed bilateral sensorineural deafness. Genetic testing of the MPZ gene showed an abnormality on denaturing gradient gel electrophoresis analysis in exons 3a and 3b corresponding to codons 79–150. Subsequent DNA sequence analysis revealed a heterozygous base change causing an amino acid change of threonine (Thr) to methionine (Met) at position 124, this mutation mapping to the extracellular loop of the MPZ protein. The patient was treated in the acute phase with a course of intravenous methylprednisolone, which improved her weakness and sensory symptoms substantially within weeks. She, however, over the following 12 months developed severe bladder dysfunction with urinary retention, which required insertion of a Address correspondence to: Dr. Yusuf A. Rajabally, Neuromuscular Clinic, Department of Neurology, University Hospitals of Leicester, Leicester General Hospital, Leicester LE5 4PW, UK. Tel: þ44-116258-4574; Fax:þ44-116-258-4875; E-mail: yusuf.rajabally@uhl-tr.nhs.uk Journal of the Peripheral Nervous System 10:388–389 (2005)

Electrophysiological predictors of steroidresponsiveness in chronic inflammatory demyelinating polyneuropathy

Sirs: There are, to our knowledge, no established indicators of steroid-responsiveness in chronic inflammatory demyelinating polyneuropathy (CIDP). We retrospectively reviewed the records of 23 patients with CIDP, treated with high-dose steroids, to ascertain the presence of markers of treatment-responsiveness. All had a clinical diagnosis of CIDP made on the basis of a recurrent or progressive motor and sensory disturbance developing over more than 2 months, with hypo/areflexia. All fulfilled at least one set of published electrodiagnostic criteria [1, 4–6, 11, 13]. We excluded patients who had concomitantly received intravenous immunoglobulins or LETTER TO THE EDITORS

Vertical optokinetic nystagmus in Parkinson's disease.

Parkinsons disease (PD) is associated with a number of oculomotor deficits; however, little is known about changes in vertical optokinetic nystagmus (OKN) associated with PD. We recorded eye movements in 14 PD patients and 14 age‐matched controls in response to large field OKN stimulation using stimulus velocities of 20°/second and 40°/second. We compared asymmetry of horizontal and vertical responses in the two groups. We found vertical OKN to be strongly asymmetric in PD with reduced gains for downward‐moving stimuli. This asymmetry was significantly greater than that recorded in control volunteers. We postulate that this could result from an abnormal pursuit/early OKN system in PD leading to greater influence of the delayed OKN system.

Chronic inflammatory demyelinating polyneuropathy associated with alopecia totalis and Sjögren syndrome

Chronic inflammatory demyelinating polyneuropathy (CIDP) can present in the context of several autoimmune conditions. Sj€ ogren syndrome (SS) is a systemic autoimmune disease that has been associated with peripheral neuropathy, mainly a sensory axonal neuropathy or neuronopathy with variable prevalence. Here, we report a case of a woman who developed in succession alopecia totalis, CIDP with predominantly motor involvement, and finally, SS. This 58-year-old Caucasian woman presented with gradual onset of limb weakness. She had a history of autoimmune alopecia since age 25 with alopecia totalis and hypothyroidism due to goiter. In her family, one of her sisters had alopecia areata, and one maternal aunt had rheumatoid arthritis. Blood tests showed normal metabolic and autoimmune screening apart from mildly reduced vitamin B12 levels with negative anti-parietal cell antibodies. Epstein-Barr virus, Cytomegalovirus and Campylobacter jejuni serology were consistent with antecedent, unrelated, infections. Anti-ganglioside antibodies were negative. Cerebrospinal fluid analysis showed only marginally raised proteins (0.49 g/L) with normal cell counts. Nerve conduction studies (Table 1) showed a demyelinating neuropathy with predominant involvement of the upper limbs (where velocities were reduced and conduction blocks were present), and a degree of motor axonal loss in the lower limbs. MRI of the lumbar spine with gadolinium showed enhancement of the lumbar roots bilaterally. She fulfilled previous and current electrophysiological criteria for a ‘‘probable’’ diagnosis of CIDP, with pure motor involvement. She was treated with a course of intravenous immunoglobulin (IVIg), which resulted in marked improvement of her motor function. She subsequently required regular IVIg infusions to maintain her clinical motor improvement. Over the following year she noticed dryness of the eyes and mouth. She developed mild sensory symptoms only in the upper limbs. Neurological examination showed reduced vibration sense up to proximal levels in all four limbs with preserved proprioception. Repeat blood tests showed positive anti-Ro/SSA antibodies with negative ANA. A lip biopsy showed chronic sialoadenitis consistent with SS. To date, the association of CIDP and autoimmune alopecia is very rare. In the only reported case, alopecia universalis developed a few months before CIDP. In our patient there was a 33-year gap. Intervals of decades between the development of multiple autoimmune conditions are not unusual. Of interest, the hair follicle is a site of relative immune privilege similar to the peripheral nervous system, and alteration of the mechanism of immune privilege is thought to lead to hair loss typical of alopecia areata and universalis. It is noteworthy that inflammatory motor neuropathies are rarely described with SS. Our patient presented with a purely motor form of CIDP and developed sensory features concomitantly with the onset of SS. To our knowledge, CIDP has only rarely been described in association with SS, and pure motor neuropathic involvement is exceptional in SS. In conclusion, clustering of autoimmune disorders in the same individual is a well-known phenomenon and is thought to depend on genetic factors. The recognition of these associations is important, as it can suggest common pathogenetic mechanisms and lead to better understanding of autoimmune diseases.

Charcot‐Marie‐Tooth disease type 1A associated with acute porphyric neuropathy

Sir, A 26-year-old woman was admitted with an insidious history of abdominal pain and nausea. Three days later she noticed tingling and sharp pains in both legs and back, progressing on to quadriparesis. She denied any preceding illness, drug or toxin exposure. Examination revealed bilateral pes cavus with normal higher mental and cranial nerve functions. Motor strength was Medical Research Council (MRC) grade 4/5 proximally and 3/5 distally in all four limbs. There was generalized hyporeflexia with no objective sensory deficit. Clinical differential diagnoses included Guillain-Barré syndrome, porphyric neuropathy and acute postinfectious neuropathy. Intravenous immunoglobulin was given without much benefit. Routine haematological and biochemical investigations including antiganglioside anti-GM1 antibody were normal or negative. CSF showed an initial lymphocytic pleocytosis of 70, which normalized in 3 weeks. CSF protein was normal. Campylobacter jejuni serology was negative. Electrophysiology showed demyelinating sensorimotor neuropathy with severe homogenous slowing of motor velocities with associated axonal involvement (Table 1). Urine porphyrin screening was positive. Total porphyrin level was 20284 nM (normal 20–320 nM), 81% of which was uroporphyrin. Porphobilinogen was 479 lM (0–10.2). Red cell PBG deaminase levels were 26 nmol/h/ml RBC (normal 24–67). Nonsense mutation (R225X) was identified in exon 12 of HMBS gene. The patient was commenced on a course of haeme arginate with gradual improvement in the motor function, of at least one MRC grade, in all affected limbs. In view of the pes cavus and unexplained predominantly demyelinating neuropathy with homogeneous slowing of motor nerve conduction velocities suggestive of genetic neuropathy [1], the patient was further investigated. Genetic testing showed duplication of the p11.2 region of chromosome 17, consistent with a diagnosis of Charcot-Marie-Tooth disease (CMT) type 1A. Examination of immediate family members only showed pes cavus in her father, who did not have electrophysiology.