Focal Central Nervous System Disorders

The Peripheral Neuropathy Solution

Peripheral Neuropathy Program By Dr. Randall Labrum

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The clinical profile of CNS abnormalities described in association with pSS is similar to that reported in CNS lupus, and includes optic neuropathy, hemiparesis, movement disorders, brainstem and cerebellar syndromes, recurrent transient ischemic attacks, and motor neuron syndrome. Differentiation between SLE and pSS with CNS involvement can be particularly difficult, as focal neurologic deficits, oligoclonal bands in the cerebral spinal fluid (CSF), and abnormalities on MRI are detected in both SLE and SS patients.4,5,34 The prevalence of serious focal and multifocal CNS involvement is low, in the range of 2% to 10% in multiple studies, particularly in those studies that assessed the frequency of CNS disorders among patients referred to rheumatology clinics.5,9,20,22,27,33,34

Spinal cord syndromes reported in pSS include transverse myelitis and progressive myelopathy, resembling primary progressive multiple sclerosis.4,5,41 Both isolated optic neuritis and myelopathy have been described in pSS patients who are seroneg-ative.42 Case reports of pSS presenting with isolated optic neuropathy suggest consideration of pSS in the differential diagnosis of optic neuropathy.43,44 Neuromyelitis optica (NMO, also known as Devic's syndrome) is an inflammatory neurologic disease characterized by recurrent episodes of myelitis and optic neuritis. NMO has been reported in association both with SLE and with pSS (Fig. 1), but it is unclear whether the association is beyond that expected by chance. A recent report described two cases of pSS among 153 consecutive patients with confirmed or suspected NMO, a prevalence (1.3%) marginally higher than that of pSS in the general population.45 However, the cases of pSS were identified by prior diagnosis rather than prospective evaluation for SS, thus the co-occurrence of pSS and NMO may be higher than suggested by this study.

Sjogren Brain Mri

Fig. 1. MRI of a 23-year-old woman with pSS and neuromyelitis optica. The patient has a history of bilateral optic neuropathy and has had recurrent episodes of myelitis since age 11. (A) Cervical spine MRI shows a gadolinium-enhancing cord lesion extending from C7-T4 (white arrow). Brain MRI shows T2-hyperintense lesions in the corpus callosum (B) and in the subcortical and periventricular white matter (C) (black arrows).

Fig. 1. MRI of a 23-year-old woman with pSS and neuromyelitis optica. The patient has a history of bilateral optic neuropathy and has had recurrent episodes of myelitis since age 11. (A) Cervical spine MRI shows a gadolinium-enhancing cord lesion extending from C7-T4 (white arrow). Brain MRI shows T2-hyperintense lesions in the corpus callosum (B) and in the subcortical and periventricular white matter (C) (black arrows).

Primary Sjogren's syndrome can mimic or coexist with multiple sclerosis (MS),42'46'47 thereby presenting significant diagnostic and therapeutic dilemmas. Alexander and colleagues46 reported an unusual series of 20 pSS patients with multifocal neurologic disease in whom the clinical features, evoked potentials, and CSF fluid profiles met criteria for definite MS, although a high proportion of these patients had features of systemic disease (cutaneous vasculitis, peripheral neuropathy, and myositis) not found in MS patients. De Seze and colleagues48 studied 60 consecutive patients with the relatively rare primary progressive form of MS, 10 of whom (17%) met criteria for pSS. Other studies of MS populations have not found unequivocally higher prevalence of pSS than that expected in the general population.49-51

A much stronger association between pSS and MS was reported by Wang and colleagues,47 who found that 6 of 12 consecutive Taiwanese patients with relaps-ing-remitting MS also met AECG criteria for pSS. However, many if not most of these patients appear to have had the optic-spinal variant of MS, which is particularly frequent in the Asian population and thought to represent NMO rather than MS.52,53 Ultimately, a statistical association between pSS and MS or NMO remains suspected but unproven.

Peripheral Nervous System Involvement

As is the case with CNS involvement, neuropathy can be the presenting feature of pSS.4,9,54,55 Neuropathic symptoms preceded sicca symptoms in about 40% of the patients described by Mellgren and colleagues.7 Grant and colleagues56 described patients with neuropathy and mild sicca who did not develop other extra-glandular manifestations of pSS over long-term follow-up, despite evidence of pSS on minor salivary gland biopsy. Classification of such patients is difficult, as the evolution of pSS has been observed as long as 12 years following presentation with neuropathy.57 Sensory neuronopathy, in which the primary pathology is in the cell body in the dorsal root or trigeminal ganglion rather than the axon, is considered distinctive of pSS. In addition, sensorimotor neuropathies, sensory neuropathies, cranial neuropathies, autonomic neuropathy, and mononeuropathy multiplex have been reported.4,5,7,9,57-59 While sensory and sensorimotor neuropathies are the most frequently reported type of peripheral nervous system involvement, there are also case reports of acute (Guillain Barré syndrome)60 and chronic demyelinating polyneuropathy.5

Differences in the profile of peripheral nervous system involvement in various studies are attributable to differences in patient selection criteria and diagnostic approaches. For example, in a recent population-based study, the predominant abnormality was prolongation of F-wave latencies interpreted as evidence of subclin-ical demyelinating motor neuropathy. Small fiber sensory neuropathy was rare in this cohort.61 By contrast, series originating in neurology clinics57 indicate that sensory predominant neuropathy or sensory neuronopathy are the most common presentation among patients with pSS and peripheral nervous system disease.

In pSS patients with peripheral nervous system involvement, the predominant clinical manifestation may depend on whether the dorsal root sensory ganglion is the primary target or the perivascular endoneurial wall. Evolution over time of small fiber neuropathy developing into a sensory ataxic neuronopathy has been reported and suggests that, at least in some pSS patients, inflammation within the dorsal root ganglion initially affects the neurons that convey small fiber modalities.57 Clinical pathologic correlation has suggested that in the majority of cases, sensory ataxia, painful sensory neuropathies, and trigeminal neuropathy are related to a sensory ganglionitis, whereas mononeuritis multiplex and multiple cranial neuropathies are more closely associated with a peripheral nerve vasculitis.54,57,62,63 In 558 consecutive pSS patients evaluated by Ramos-Casals and colleagues,10 peripheral neuropathy was strongly associated with the presence of cutaneous vasculitis (31% versus 4%, P<.001).

Dysfunction of small-caliber neurons may be far more common than suggested by previous studies. Burning pain, pain on light stroking of the skin, attacks of pain without seeming provocation, and subtle sensory deficits are features of a neuropathic process that may be under-recognized in patients with SS. In a recent large survey of pSS patients, 70% reported symptoms suggestive of neuropathic pain. Symptoms were significantly more often reported by pSS patients than age- or gender-matched controls after controlling for fibromyalgia and depression, suggesting that subclinical painful sensory neuronopathy or neuropathy may be quite frequent.64


Histopathologic descriptions of nervous system disorders in pSS patients are rare.65-67 In a small series of patients with sensory ataxia who were studied with spinal cord MRI, high-intensity T2 abnormalities were found in the posterior columns of the cervical cord in 12 of 14 patients, 2 of whom had a necrotizing vasculitis.68 Case reports of postmortem examination of a patient with recurrent transverse myelitis demonstrated angiitis and necrosis in the cervical and thoracic spinal cord but not elsewhere in the CNS.69,70 Cerebral vasculitis is very rarely reported in pSS. In Alexander and colleagues' series,71 focal clinical CNS disease was associated with brain infarcts and angiographic evidence of small vessel angiitis. MRI findings in patients with active CNS disease and SS are typically that of diffuse small foci of hyperintensity on T2-weighted imaging, suggestive of small vessel disease.

Small vessel disease can also lead to subtle cognitive dysfunction and result in impairment in attention and executive function, typically with preservation of memory. However, vasculopathy is unlikely to be the only mechanism leading to cognitive dysfunction in patients with pSS. Cognitive impairment is also detected in the absence of MRI abnormalities suggestive of vascular lesions in pSS. Single photon emission computed tomography imaging of pSS patients with normal brain MRI and neuropsychiat-ric involvement demonstrated lesions compatible with cerebral hypoperfusion in 56%.72 Based on this study, it seems likely that pathogenic mechanisms other than vasculopathy will be found in as many as 45% of SS patients with CNS involvement, particularly those with subtle cognitive impairment.

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  • cailyn
    What is focal central nervous system ischemia?
    2 years ago

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