Mohamed Mahdi-Rogers

Epidemiology of chronic inflammatory neuropathies in southeast England

There is little information about the prevalence and disease burden of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and paraproteinaemic demyelinating neuropathy (PDN).

Humoral and cellular immune responses to myelin protein peptides in chronic inflammatory demyelinating polyradiculoneuropathy

Objectives: Evidence that chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease was sought, by studying cellular and humoral immune responses to peripheral nerve myelin proteins. Methods: 40 CIDP, 36 healthy control subjects (HC) and subjects with non-immune mediated neuropathies (other neuropathies, ON) for antibodies were studied by ELISA and cellular responses by cytokine ELISPOT (INFγ, IL10) and ELISA (IL17) to synthetic peptides representing P0, P2 and PMP22. Results: Antibodies to P0, P2 or PMP22 peptides were detected in only a minority of CIDP, both not treated (nT-CIDP) and treated (T-CIDP). IgG antibodies to P280–105 were significantly more frequent in CIDP than in HC (4/30 vs 0/32; p<0.05) but the difference from ON (1/25) was not significant. In ELISPOT assays, IFNγ was detected at a low frequency in CIDP and did not differ from HC or ON. In contrast, IL10 responses against P21–85 were more frequent in nT and T-CIDP (7/24 and 3/16) than HC (0/36; p<0.001 and p<0.05, respectively). The production of IL17 in cell-culture supernatants was not increased. Conclusions: Antibodies to non-conformational antigenic epitopes of myelin proteins rarely occur in CIDP. None of the myelin protein peptides elicited IFNγ responses, but P2 elicited IL10 responses significantly more often in CIDP patients than in controls. This reactivity may be part of an antigen-specific Th2 type pathogenetic or regulatory mechanism or represent a transitory epiphenomenon due to nerve damage. In our study, P2 was the protein antigen most likely to be involved in the aberrant immune responses in CIDP.

Autologous peripheral blood stem cell transplantation for chronic acquired demyelinating neuropathy

Six patients with chronic acquired demyelinating neuropathy (CADP) were treated with autologous peripheral blood stem cell transplantation (PBSCT). Two with polyneuropathy, organomegaly, endocrinopathy, M‐protein, and skin changes (POEMS) syndrome improved–improvement was sustained in one but relapsed and required repeat transplant in the other. Two of the three with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and one with an IgM paraprotein and antibodies to nerve improved–of the responders, one relapsed after 18 months and the other was in remission after 6 months. Four developed neutropenic septicemia and pneumonia. The role of PBSCT in CADP refractory to other treatment deserves further investigation but the serious adverse events and lack of sustained response in some patients emphasize the need for caution.

Economic costs and quality of life in chronic inflammatory neuropathies in southeast England

Cost‐of‐illness studies and health‐related quality of life (HRQoL) measurements are needed to assess the effects of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and paraproteinaemic demyelinating neuropathy (PDN) on society.

Chronic inflammatory demyelinating polyradiculoneuropathy: a role for haematopoietic stem cell transplantation?

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical syndrome of a chronic progressive or relapsing and remitting, symmetrical, sensory and motor radiculoneuropathy. The immune reaction in CIDP is characterised by selective inflammation of peripheral nerves and is probably due to the interaction of cellular and humoral responses. Only three treatments for CIDP have demonstrated benefit in randomised studies, corticosteroids, plasma exchange and intravenous immunoglobulin. 25% of patients fail to respond or do not respond adequately to these treatments. Experimental data in animal models have shown that several autoimmune disorders, either congenital or acquired, can be transferred and/or treated by the transplantation of bone marrow stem cells. Haematopoietic stem cell transplantation (HSCT) has been performed with varying success in over 700 patients with autoimmune disorders throughout Europe. The experience in CIDP is very limited. This article will review current understanding of CIDP and experience of the use of HSCT in refractory CIDP.

A Man with Episodes of Shoulder Pain and a Weak Arm

A 69 year old man presents with a history of recurrent episodes of brachial neuritis. The symptoms started at the age of 35 and the episodes were usually preceded by flu-like illnesses or infection. His son had an episode of brachial neuritis at the age of 17. The clinical picture is consistent with hereditary neuralgic amyotrophy (HNA), however genetic testing does not reveal mutations in the Septin 9 (SEPT9) gene. As only ~ half of the HNA families studied had a defect in the SEPT9 gene, mutations in other genes that have not yet been identified may be responsible for HNA.

A Man with a Pacemaker Develops Difficulty Walking

A 66 year old man presents with a two year history of gradually progressive lower limb weakness. The presentation was preceded by symptoms compatible with bilateral carpal tunnel syndrome. Four years before the development of neurological symptoms he had a permanent pacemaker inserted. Amyloid deposits were detected on sural nerve biopsy. A mutation in the transthyretin gene (Val30Met) confirms the diagnosis of Familial amyloid polyneuropathy.

A Woman with Burning Hands

A 59 year old woman presents with a 3 year history of burning sensations in the hands and feet. There is neither limb weakness nor autonomic symptoms. Nerve conduction studies and thermal thresholds are normal. Her father was reported to have Fabry disease. Genetic testing confirms the presence of a heterozygous mutation in the alpha-galactosidase gene.

A Man with Painful Feet and Hand Ulcers

A 49 year old man presents with a 20 year history of progressive numbness, shooting pain and weakness affecting the upper and lower limbs. He also has recurrent ulcers. His mother had a painful sensory neuropathy. Nerve conduction studies are compatible with a sensory and motor axonal neuropathy. Genetic testing reveals a mutation in the SPTLC1 gene confirming the diagnosis of Hereditary Sensory and Autonomic Neuropathy (HSAN) type 1A.

A Woman Who Could Not Wear High Heels

A 44 year old woman with a positive family history for neuromuscular disease, presents with a slowly progressive peripheral neuropathy, found to be demyelinating on neurophysiology. Genetic testing confirms the diagnosis.