Invited review: peripheral neuropathy in Sjogren's syndrome

Our experience and review of the literature reveal that Sjogren's syndrome (SS) is an important, poorly recognized cause of peripheral neuropathy. Several forms of peripheral nerve dysfunction occur in SS including trigeminal sensory neuropathy, mononeuropathy multiplex, distal sensory neuropathy, distal sensorimotor peripheral neuropathy and a pure sensory neuronopathy syndrome. Rarely, chronic relapsing inflammatory polyneuropathy and multiple cranial neuropathies appear. Clinical evidence of glandular involvement is often minimal or absent when patients with SS develop peripheral neuropathy; and the diagnosis of the underlying condition is elusive. We review clinical and laboratory features of this disorder and suggest appropriate evaluation of patients with neuropathy and suspected SS.     

Neuroendocrine dysfunction and response to tricyclic antidepressants

Patients with DSM-III unipolar major depression (N = 26) were treated with tricyclic antidepressants after 2 weeks of inpatient drug-free observation and neuroendocrine testing. Medication was prescribed with individualized dosages and was monitored with blood levels. Treatment response (greater than or equal to 50% decrease in Hamilton depression score after 4 weeks) was seen in 6 of 13 patients given desipramine and 7 of 13 given nortriptyline. Of the 13 nonresponders, 9 accepted treatment with another drug and/or ECT; 5 responded. Thus, 18 of the 26 patients responded to treatment. Abnormal pretreatment DST was correlated with increased responsiveness to treatment, although all patients had a high probability of response.     

Neuroendocrine dysfunction in genetic subtypes of primary unipolar depression

Disinhibited activity of the hypothalamic-pituitary-adrenocortical (HPA) neuroendocrine system, characterized most specifically by abnormal responses to the dexamethasone suppression test (DST), is observed in 40–50% of patients with endogenous depression. The heterogeneity of endogenous depressives with respect to this neuroendocrine marker is so far unexplained. A recent report from Iowa suggested that genetic factors could account for this heterogeneity, since abnormal DST responses were found with widely differing frequencies among primary unipolar depressives subtyped by the genetic criteria of Winokur. We studied 14 patients with primary endogenous delusional unipolar depression. Abnormal DST responses were found in 79% of the entire group, and with similar frequencies among each of the Winokur subtypes. In particular, five of six patients (83%) with depression spectrum disease had abnormal DST results. This contrasts with a frequency of 4% reported by the Iowa group. We conclude that disinhibited HPA activity does occur in depression spectrum disease when a delusional endogenous depression is present. Our results and those of the Iowa study could both be consistent with a threshold model of HPA activation. The high frequency of positive DST results in delusional endogenous depressives may be determined by disinhibited central pain mechanisms. Variations in this clinical dimension, combined with variations in threshold for HPA activation by pain mechanisms, could account for the heterogeneity of DST responses among endogenous depressives.     

Painful tonic/dystonic spasms in Sjogren's syndrome.

Three patients with Sjogren's syndrome are presented in whom frequent tonic/dystonic spasms of the limbs developed during the course of the illness. These patients' clinical findings suggested spinal cord involvement, a localization that was confirmed by magnetic resonance imaging in two patients. In one patient the painful movements responded to treatment with phenytoin and in one other to baclofen. Sjogren's syndrome should be considered in the differential diagnosis of conditions that produce tonic/dystonic limb spasms.     

Symptomatic periodic paralysis secondary to primary Sjogren's syndrome

INTRODUCTION: Hypokalaemic periodic paralysis can be primitive or secondary to potassium deficiency which can arise from several causes. Primary Sjogren's syndrome is a rare cause related to kidney involvement. CASE REPORT: A 50-year-old woman has been admitted for hypotonic tetraparesis which had appeared a few days earlier. History taking revealed three previous similar episodes with a notion of oral and lacrimal dryness. Laboratory tests revealed severe hypokalaemia, hyperchloremia, alkaline urinary pH and a minima 24h proteinuria. Additional investigations led to the diagnosis of a primary Sjogren's syndrome defined on the basis of international criteria. Kidney biopsy revealed tubular-interstitial nephritis. Oral corticostero?d therapy and potassium supplementation led to symptom improvement. A recurrent episode also responded to treatment. Additional urinary alkalinisation has prevented further relapse. DISCUSSION: Primary Sjogren's syndrome is an exocrine disease causing systemic disorders. Tubular-interstitial nephropathy may occur in 25 percent of patients leading to distal tubular acidosis defined by the association of hypokalaemia, hyperchloremia and alkaline urinary pH. When hypokalaemia is severe, periodic paralysis may occur. CONCLUSION: Primary Sjogren's syndrome can lead to nephropathy and subsequent hypokalaemic periodic paralysis. Urinary alkalinisation is essential to prevent this catastrophic presentation from recurring.     

Interferon alfa treatment for Sjogren's syndrome associated neuropathy

Treatment response to interferon alfa (IFNalpha) is described in three consecutive cases of two forms of Sjogren's syndrome associated neuropathy (SSN)-two with sensory ataxic ganglionopathy and one with sensorimotor neuropathy with demyelinating features. All responded well to IFNalpha in terms of neuropathic symptoms, sicca symptoms, antibody titres, and findings in salivary gland biopsy specimens. IFNalpha thus showed promise in treating both SSN and the underlying Sjogren's syndrome.     

Neuroendocrine responses in chronic schizophrenia: Evidence for serotonergic dysfunction

Neuroendocrine and mood responses to a 60 mg oral dose of the serotonin-releasing agent, fenfluramine, were assessed in ten neuroleptic-free, chronic schizophrenic patients and in age- and sex-matched normal control subjects. The prolactin (PRL) response to fenfluramine was significantly blunted in the schizophrenic subjects. Growth hormone and cortisol levels were not differentially affected by the challenge. There was no significant effect of fenfluramine on mood in either group. The blunted PRL response in the schizophrenic group suggests serotonergic dysfunction; possible mechanisms of this finding and implications for treatment are considered.     

Primary Sjogren's syndrome presenting as a generalized chorea

We report on a patient who presented with generalized chorea as the first manifestation of Sjogren Syndrome, and review the possible pathogenesis.     

An atypical case of mononeuritis multiplex in primary Sjogren's syndrome

We present an atypical case of peripheral nervous system (PNS) involvement in Sjogren's syndrome in a 63 year-old woman. Symptoms of an entrapment neuropathy were the first manifestation of the systemic disease and they were subsequently coupled to those of a mononeuritis multiplex. Clinical and laboratory signs for the diagnosis of Sjogren's syndrome became subsequently overt. The mononeuritis multiplex remained clinically limited to the upper limbs and characterized by unusually severe motor symptoms which progressed up to the development of a final complete deplegia. By contrast, sensory symptoms at the upper limbs remained mild over the entire course of the disease and the lower limbs revealed a subclinical sensory-motor damage only during the late stage.     

Neuroendocrine aspects of chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the neuroendocrine system. A symposium was organized in March 2001 to explore the possibility of an association between neuroendocrine dysfunction and CFS, with special emphasis on the interactions between neuroendocrine dysfunction and other abnormalities noted in the immune and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.     

Neuroendocrine dysfunction in schizophreniform disorder: correlation with six-month clinical outcome

The thyrotropin-releasing hormone (TRH) stimulation test and the dexamethasone suppression test (DST) were administered to 21 patients with schizophreniform disorder at the time of admission for acute illness: 9 showed dysregulation on one or the other test. Seventeen patients followed for 6 months were divided into two groups: those with persistent dysfunction and/or psychotic symptoms and those in full remission. Only 1 of 7 patients (14%) with persistent dysfunction in contrast to 7 of 10 patients (70%) in full remission revealed dysregulation on either test. Neuroendocrine challenges may be useful in the early assessment of first-break psychotic patients, and neuroendocrine dysregulation may be a predictor of episodic illness with a better prognosis.     

干燥综合征患者伴神经系统损害7例临床及病理变化

目的 探讨干燥综合征患者伴神经系统损害患者的临床及其肌肉和周围神经病理改变。方法 对7例患者的临床表现、实验室检查进行系统描述,对肌肉及神经组织进行组织学及组织化学染色,并行电子显微镜检查。结果 2例神经组织活检可见有髓神经纤维严重脱失,有髓神经纤维数目严重减少,轻度轴索变性。5例肌肉活检可见肌纤维萎缩、坏死,血管周围有单核样细胞浸润,肌内衣有微血管炎的病理改变。结论 干燥综合征患者的肌肉或周围神经并发症在疾病的早期即可出现,肌肉或神经活检可证实有无损害及其严重程度,早期诊断及早期治疗对改善干燥综合征患者伴神经系统损害者的预后是很有 必要的。     

Sensory ataxic neuropathy and esophageal achalasia in a patient with Sjogren's syndrome

We describe a patient who developed an ataxic sensory syndrome associated with xerophthalmia and progressive dysphagia with regurgitation. Electrophysiological findings were consistent with an axonal sensory neuropathy, and superficial peroneal nerve biopsy showed a reduction in number of myelinated fibers with epineurial inflammation. Rheumatoid factor, anti-SSA/SSB and antinuclear antibodies were positive and a diagnosis of Sjogren's syndrome was made. An endoscopic investigation revealed esophageal achalasia. We suggest that there may be a common autoimmune mechanism directed to different targets on the basis of this rare association.