BRIEF COMMUNICATIONS
The Treatable Dementia of Sjogren’s Syndrome Richard J. Caselli, MD,’ Bernd W. Scheithauer, MD,? Carolyn A. Bowles, MD,S Max R. Trenerry, PhD,§ Fredric B. Meyer, MD,‘Jeffrey S. Smigielski, PhD,5 and Moses Rodriguez, MD+
Progressive dementia developed during a 15-month period in a 56-year-old woman with serologically and clinically documented primary Sjogren’s syndrome. Findings from magnetic resonance imaging and angiography were normal, but a brain biopsy disclosed perivascular lymphocytic inflammation in leptomeningeal and parenchymal vessels. Treatment with high-dose corticosteroids produced rapid and nearly complete resolution of the dementia. Caselli RJ, Scheithauer BW, Bowles CA, Trenerry MR, Meyer FB, SmigielskiJS, Rodriguez M. The treatable dementia of Sjogren’s syndrome. Ann Neurol 1991;30:98-101
Primary Sjogren’s syndrome is defined by the symptom complex of xerophthalmia and xerostomia, but neurological complications El, 2) suggest that the underlying pathophysiology is not restricted to the lacrimal and salivary glands. Small-vessel arteritis may produce acute meningoencephalitis that can rapidly progress to coma and death despite the administration of corticosteroids [1-51. Mild cognitive deficits have been described in selected series of patients without meningoencephalitis, consisting primarily of impaired attention and concentration 16, 71, but primary Sjogren’s syndrome has not been proved to cause dementia. We now report the first documented case of dementia caused by primary Sjogren’s syndrome and describe its successful treatment with oral corticosteroids.
Patient Report A 56-year-old, left-handed woman had a 16-year history of treated hypothyroidism and Sjogren’s syndrome (dry eyes and mouth) with absence of tear production for 15 years. She was noted by her husband and co-workers to be forgetful at home and on the job. She managed the computer of a small business and lost her ability to program the computer
From the *Department of Neurology, +Section of Surgical Pathology, $Division of Rheumatology and Internal Medicine, #Section of Psychology, and ”Department of Neurologic Surgery, Mayo Clinic and Mayo Foundation, Rochester, MN. Received Sep 18, 1990, and in revised form Dec 26. Accepted for publication Jan 1, 1991. Address correspondence to Dr Cascili, Mayo Clinic Scoctsdale, 13400 East Shea Boulevard, Scottsdale, A 2 85259.
and to correct computer failures. Her forgetfulness worsened initially but then improved so that 6 months after onset she regained the ability to operate and repair the computer. Eight months after onset she again lost these abilities, only to regain them 1 month later. Eleven months after onset, visual hallucinations developed (seeing “bugs and worms”) and she began hiding her medications. This prompted admission to a psychiatric hospital where she was treated with a succession of neuroleptic and antidepressant drugs and was first observed to have a mild static tremor. Her erythrocyte sedimentation rate was 80 mm in 1 hour (Westergren method). Magnetic resonance imaging of the brain, spinal fluid examination, and cerebral angiography gave normal results. Alzheimer’s disease was diagnosed, and her cognitive deterioration continued. Fifteen months after onset she came to the Mayo Clinic (Rochester, MN). At that time, her only medications were thyroid supplementation and transdermal estrogen. There was no medical history of arthritis, rash, or nephritis, but she related a past history of parotid gland enlargement. Her general physical examination was remarkable for xerostomia, keratoconjunctivitis sicca, and the absence of any large artery bruits, arthropathy, o r rash. Neurological examination was notable for mild, symmetrical hyperreflexia including a jaw jerk; bilateral Babinski signs; a mild static and terminal appendicular tremor; and an unsteady normal-based gait, which did not resemble the gait apraxia of patients with normal-pressure hydrocephalus. She was slow to respond verbally and to perform written tasks, had perseverative, hesitant speech with occasional phonemic paraphasias (e.g., “battellack” for “Cadillac”),and was anisodiaphoretic. She was not anomic, however, and memory impairment appeared commensurate with her inattention. She learned four words after two trials, and was able to recall all four after 5 minutes. She scored 27 of 38 on the Short Test of Mental Status f8], consistent with the diagnosis of dementia, and - 15 on the Benton Orientation questionnaire {9}, indicative of severe temporal disorientation. Salient abnormalities included an increased erythrocyte sedimentation rate of 48 mm in 1 hour, the presence of anti-SSA and anti-SSB antibodies, an increased rheumatoid factor of 63 I IU/ml, polyclonal elevation of serum and cerebrospinal fluid (CSF) immunoglobulins, a mildly elevated CSF total protein value, a single unique oligoclonal band in the CSF, and an elevated calculated CSF synthesis rate of 3 1.76 mg/24 hr. Antinuclear antibodies and anti-dsDNA antibodies were negative, and the serum complement was normal. Rose bengal stain of her corneas was abnormal. These abnormalities were compatible with the diagnosis of primary Sjogren’s syndrome and demonstrated the presence of a systemic inflammatory state. Electroencephalography performed 6 months after the onset of cognitive decline revealed diffuse, nonspecific, severely dysrhythmic slowing (dysrhythmia grade 3, generalized, nonspecific). Electroencephalography performed 15 months after onset revealed further deterioration (dysrhythmia grade 3 , generalized, nonspecific; and delta grade 1, generalized). Magnetic resonance images obtained at 11 and 15 months after onset of cognitive decline were entirely normal. Bilateral carotid angiography revealed no evidence of vasculitis and only minimal atherosclerotic changes. Scores on the Wechsler Adult Intelligence Scale-Revised
98 Copyright 0 1991 by the American Neurological Association
Newopsycbologic Data Cognitive Function
Test
Prebiopsy
General intellect
Temporal orientation WAIS-R VIQ WAIS-R PIQ DRS WMS-R Verbal Index AVLT LOT AVLT delayed recallitrial 5 AVLT intrusion errors WMS-R Visual Index Complex Figure Copy Complex Figure Recall MAE Token Test MAE COWA WCST-categories completed WCST-perseverative errors
-15
Verbal memory
Visual memory
Language Abstract reasoning
90 64 110 84
17 015 19
The Treatable Dementia of Sjogren’s Syndrome Richard J. Caselli, MD,’ Bernd W. Scheithauer, MD,? Carolyn A. Bowles, MD,S Max R. Trenerry, PhD,§ Fredric B. Meyer, MD,‘Jeffrey S. Smigielski, PhD,5 and Moses Rodriguez, MD+
Progressive dementia developed during a 15-month period in a 56-year-old woman with serologically and clinically documented primary Sjogren’s syndrome. Findings from magnetic resonance imaging and angiography were normal, but a brain biopsy disclosed perivascular lymphocytic inflammation in leptomeningeal and parenchymal vessels. Treatment with high-dose corticosteroids produced rapid and nearly complete resolution of the dementia. Caselli RJ, Scheithauer BW, Bowles CA, Trenerry MR, Meyer FB, SmigielskiJS, Rodriguez M. The treatable dementia of Sjogren’s syndrome. Ann Neurol 1991;30:98-101
Primary Sjogren’s syndrome is defined by the symptom complex of xerophthalmia and xerostomia, but neurological complications El, 2) suggest that the underlying pathophysiology is not restricted to the lacrimal and salivary glands. Small-vessel arteritis may produce acute meningoencephalitis that can rapidly progress to coma and death despite the administration of corticosteroids [1-51. Mild cognitive deficits have been described in selected series of patients without meningoencephalitis, consisting primarily of impaired attention and concentration 16, 71, but primary Sjogren’s syndrome has not been proved to cause dementia. We now report the first documented case of dementia caused by primary Sjogren’s syndrome and describe its successful treatment with oral corticosteroids.
Patient Report A 56-year-old, left-handed woman had a 16-year history of treated hypothyroidism and Sjogren’s syndrome (dry eyes and mouth) with absence of tear production for 15 years. She was noted by her husband and co-workers to be forgetful at home and on the job. She managed the computer of a small business and lost her ability to program the computer
From the *Department of Neurology, +Section of Surgical Pathology, $Division of Rheumatology and Internal Medicine, #Section of Psychology, and ”Department of Neurologic Surgery, Mayo Clinic and Mayo Foundation, Rochester, MN. Received Sep 18, 1990, and in revised form Dec 26. Accepted for publication Jan 1, 1991. Address correspondence to Dr Cascili, Mayo Clinic Scoctsdale, 13400 East Shea Boulevard, Scottsdale, A 2 85259.
and to correct computer failures. Her forgetfulness worsened initially but then improved so that 6 months after onset she regained the ability to operate and repair the computer. Eight months after onset she again lost these abilities, only to regain them 1 month later. Eleven months after onset, visual hallucinations developed (seeing “bugs and worms”) and she began hiding her medications. This prompted admission to a psychiatric hospital where she was treated with a succession of neuroleptic and antidepressant drugs and was first observed to have a mild static tremor. Her erythrocyte sedimentation rate was 80 mm in 1 hour (Westergren method). Magnetic resonance imaging of the brain, spinal fluid examination, and cerebral angiography gave normal results. Alzheimer’s disease was diagnosed, and her cognitive deterioration continued. Fifteen months after onset she came to the Mayo Clinic (Rochester, MN). At that time, her only medications were thyroid supplementation and transdermal estrogen. There was no medical history of arthritis, rash, or nephritis, but she related a past history of parotid gland enlargement. Her general physical examination was remarkable for xerostomia, keratoconjunctivitis sicca, and the absence of any large artery bruits, arthropathy, o r rash. Neurological examination was notable for mild, symmetrical hyperreflexia including a jaw jerk; bilateral Babinski signs; a mild static and terminal appendicular tremor; and an unsteady normal-based gait, which did not resemble the gait apraxia of patients with normal-pressure hydrocephalus. She was slow to respond verbally and to perform written tasks, had perseverative, hesitant speech with occasional phonemic paraphasias (e.g., “battellack” for “Cadillac”),and was anisodiaphoretic. She was not anomic, however, and memory impairment appeared commensurate with her inattention. She learned four words after two trials, and was able to recall all four after 5 minutes. She scored 27 of 38 on the Short Test of Mental Status f8], consistent with the diagnosis of dementia, and - 15 on the Benton Orientation questionnaire {9}, indicative of severe temporal disorientation. Salient abnormalities included an increased erythrocyte sedimentation rate of 48 mm in 1 hour, the presence of anti-SSA and anti-SSB antibodies, an increased rheumatoid factor of 63 I IU/ml, polyclonal elevation of serum and cerebrospinal fluid (CSF) immunoglobulins, a mildly elevated CSF total protein value, a single unique oligoclonal band in the CSF, and an elevated calculated CSF synthesis rate of 3 1.76 mg/24 hr. Antinuclear antibodies and anti-dsDNA antibodies were negative, and the serum complement was normal. Rose bengal stain of her corneas was abnormal. These abnormalities were compatible with the diagnosis of primary Sjogren’s syndrome and demonstrated the presence of a systemic inflammatory state. Electroencephalography performed 6 months after the onset of cognitive decline revealed diffuse, nonspecific, severely dysrhythmic slowing (dysrhythmia grade 3, generalized, nonspecific). Electroencephalography performed 15 months after onset revealed further deterioration (dysrhythmia grade 3 , generalized, nonspecific; and delta grade 1, generalized). Magnetic resonance images obtained at 11 and 15 months after onset of cognitive decline were entirely normal. Bilateral carotid angiography revealed no evidence of vasculitis and only minimal atherosclerotic changes. Scores on the Wechsler Adult Intelligence Scale-Revised
98 Copyright 0 1991 by the American Neurological Association
Newopsycbologic Data Cognitive Function
Test
Prebiopsy
General intellect
Temporal orientation WAIS-R VIQ WAIS-R PIQ DRS WMS-R Verbal Index AVLT LOT AVLT delayed recallitrial 5 AVLT intrusion errors WMS-R Visual Index Complex Figure Copy Complex Figure Recall MAE Token Test MAE COWA WCST-categories completed WCST-perseverative errors
-15
Verbal memory
Visual memory
Language Abstract reasoning
90 64 110 84
17 015 19
