the combination of ataxia and peripheral neuropathy ( pn ) may be associated with a variety of conditions such as paraneoplastic syndromes , celiac disease ( cd ) , sjogren s syndrome , chronic inflammatory demyelinating polyneuropathy , and miller - fisher syndrome , ( honnorat et al 2001 ; lang et al 2003 ; koller et al 2005 ) . cd is a multigenetic t - cell mediated autoimmune disease where intolerance develops to the dietary protein gluten. cd typically presents with gastrointestinal manifestations but in some cases ataxia can be the presenting sign . other extraintestinal manifestations include iron - deficiency anemia , osteoporosis , cryptogenic hypertransaminasemia , recurrent abortion , autoimmune diseases which are now recognized to be more common in the absence of gastrointestinal symptoms in patients with gluten - sensitive enteropathy . it has been estimated from prevalence studies that for every patient with cd who presents with gartrointestinal symptoms , there are eight patients with silent disease . since diabetes is a major cause of pn ( dyck et al 1993 ; vinik et al 2006 ) there is complacency about seeking alternative causes of neurological syndromes in such patients . autoimmune pathogenetic mechanisms have been implicated in neuropathy in diabetes ( granberg et al 2005 ) . it is unclear whether the antibodies are pathogenic or innocent bystanders ( vinik et al 2005a ) , but there is little doubt that there is a greater frequency of inflammatory demyelinating neuropathies in people with diabetes than in the general population ( sharma et al 2002 ) . the association of cerebellar ataxia and pn in diabetes has been reported in a patient with circulating gad antibodies ( iwasaki et al 2001 ) . the prevalence of cd in children with juvenile diabetes is at least 4.6% ( aktay et al 2001 ) and is known it is known to be a hall mark of type-1 diabetes . however , cd may occur in type 2 diabetes or in latent autoimmune diabetes of adult ( sanchez et al 2007 ) . we present a case of cerebellar ataxia associated with cd without gastrointestinal involvement in a patient with well - controlled diabetes in whom treatment of the autoimmunity reversed the pn , but not the ataxia . a 70-year - old caucasian male with a 3  year history of type 2 diabetes , presented with complaints of unsteadiness . he took irbersartan for hypertension and had a strong family history of type 2 diabetes but no autoimmune diseases . his musculoskeletal system showed bilateral mild wasting of the quadriceps and total loss of vibration sensation in the feet . pinprick sensation was reduced in both his lower limbs to the level of the ankles but only a mild reduction in the upper limbs . paraneoplastic antibodies , urinary heavy metal excretion , serum electrophoresis , ana , rpr , and hiv tests were negative . a mri of the spine and brain did not reveal any pathology , pet scan of the lungs for occult malignancy was negative and csf was normal . vitamin e and vitamin b12 , tsh , ceruloplasmin , and lactic acid levels were all normal . since this clinical presentation was distinctly unusual for diabetes , we investigated further for autoimmune neuropathy and incubated his serum with n1e-115 neuroblastoma cells which showed apoptotic cell death confirming the autoimmune etiology ( pittenger et al 1997 ) . electromyography showed supranormal conduction velocities over the peroneal , tibial , medial , ulnar , and sural nerves but low amplitudes indicating a mild axonal form of neuropathy . quantitative sensory testing ( qst ) revealed a mild large - fiber neuropathy with impaired vibration perception and relatively intact warm and cold thermal perception in the feet . hence , diet , exercise and oral hypoglycemic therapy were initiated to control the diabetes and in light of the strongly positive effects of his serum on immunotoxicity assay , we initiated intravenous immunoglobulin ( ivig ) therapy along with oral antioxidant therapy ( vitamin c , 500 mg / day ; vitamin e , 400 iu / day ; alphalipoic acid,1200 mg / day ; and dihomogammalinolenic acid , 3900 mg / day ) . six months later , his neuropathy had improved except for mild impairment of vibration perception . however , cerebellar signs were still present . by this time g / kg / day  2 ) but unfortunately he developed a centripetal rash after the 2nd infusion , and no further ivig was given . the patient s serum remained toxic to neuronal cells in culture despite the administration of ivig . table 1 shows the improvement in qst and autonomic nerve function tests at presentation and 17 months into treatment . these progressively worsening cerebellar signs were thought to be due to an autoimmune process , as the serum was very toxic to neuroblastoma cells . antigliadin igg , antigliadin iga and antireticulin antibodies were found to be positive among many other antibody panels that were investigated . other antibodies including , paraneoplastic antibodies , anti - gad antibodies , antithymoglobin , antimicrosomal , anti - r1 , anti - ma / ta , antiendomysial antibodies , anti - yo - antibody , anti - hu antibody , antineural antibodies ( anna-1 and anna-2 ) and lyme titers were negative ( these tests were performed by labcorp , burlington , nc ) . small bowel studies including esophagogastroduodenoscopy and biopsies of small bowel failed to show any evidence of cd . though there was no biopsy evidence of cd , he was advised to embark on a gluten - free diet based on case reports that suggested that ataxia could be the sole manifestation of cd in the absence of gastrointestinal pathology and based on antibody positivity . after 2-months on a gluten - free diet , his peripheral neuropathy showed further improvement but he still had all the signs of cerebellar dysfunction supporting the notion of different mechanisms for the cerebellar ataxia and the peripheral neuropathy . after 20 months on the diet , all the celiac antibody titers became normal and the pn showed progressive improvement but the cerebellar function did not . this patient has progressive cerebellar ataxia , improving peripheral neuropathy and decreasing titers of celiac antibodies . cerebellar ataxia could be the only manifestation of an otherwise occult cd in this patient . sensory axonal neuropathies and small fiber polyneuropathies are the most frequently reported types of peripheral neuropathy in cd ( chin et al 2003 ) . there are reports to suggest that ataxia could be the sole manifestation of cd especially in people with a genetic susceptibility ( hadjivassiliou et al 1998 ; bushara et al 2001 ) . there is growing evidence of the association of cd with many neurological disorders ( hadjivassiliou et al 1996 ) . these conditions include cerebellar ataxia , pn , epilepsy , dementia , and depression . among these , cerebellar ataxia , pn and memory impairment are the most commonly seen associations ( hadjivassiliou et al 1998 ; luostarinen et al 1999 ; pereira et al 2004 ) . there is also some suggestion that migraine , encephalopathy , chorea , brain - stem dysfunction , myelopathy , mononeuritis multiplex and guillian - barre like syndrome could be the presenting extra - intestinal manifestations of cd with or without intestinal pathology ( bushara 2005 ) . although ataxia is believed to be due to immunological damage to the cerebellum , posterior column , and peripheral nerves ( hadjivassiliou et al 1998 ) , it is unclear whether there is a common pathogenic mechanism that affects both the nervous system and the gastrointestinal tract . ataxia in cd can be due to malabsorption and associated vitamin deficiency ( hagen et al 2000 ) . there is a report where parenteral vitamin e administration improved the clinical and neurophysiological signs of cd in a vitamin e - depleted patient with this disease ( battisti et al 1996 ) . however , our patient had normal vitamin e levels and had received vitamin e. a gluten - free diet is the main modality of treatment for cd . other therapies include ivig and infliximab ( chin and latov 2005 ) . although there are reports that gluten - free diet has improved survival and quality of life , facilitated the normal growth and development in infants , prevented osteopenia and decreased the risk of t - cell lymphoma in adults , its effect on the nervous system has been variable ( leffler et al 2003 ) . there are reports where ataxia and pn persisted or even progressed with gluten free diet ( leffler et al 2003 ; chin and latov 2005 ) . our patient demonstrates a dichotomy between the responses of pn , autonomic neuropathy and cerebellar ataxia to a gluten - free diet . nonetheless the frequency of coexistence of cd in diabetes and the responsiveness of pn to therapy would encourage a search for the presence of cd in patients with diabetes and neuropathy . strikingly , the pn improved with measures to reduce autoimmunity supporting the notion that there may be an autoimmune mechanism for damage to peripheral nerves that can be resolved . unfortunately , this does not appear to be the case for the cerebellar component for reasons that are not apparent at this point in time . the occurrence of cerebellar ataxia emphasizes the need to consider cd and requires further investigation into possible pathogenetic mechanisms which appear to be distinct from that of the pn .
this is a case of a 70-year - old man with severe peripheral neuropathy , type 2 diabetes and progressively worsening cerebellar ataxia . 
 he was found to have circulating antigliadin and antireticulin antibodies compatible with celiac disease in the absence of intestinal pathology . 
 the peripheral neuropathy improved with a gluten - free diet , antioxidants and intravenous immunoglobulin , whereas the ataxia did not . 
 this case illustrates the need to test for celiac disease in patients with idiopathic ataxia and peripheral neuropathy and the need for alternative therapies for ataxia .