Neurological manifestations of Sjogren syndrome: A case series

ABSTRACT

The Sjogren syndrome is known to have a variety of manifestations apart from the classical glandular involvement. These include musculoskeletal, vascular, neurological, gastrointestinal, and renal involvement. Herein, we present a case series where patients presented with primarily with neurological complaints and retrospectively were diagnosed with Sjogren syndrome.

Introduction

Sjogren syndrome characteristically involves glandular organs like salivary and lacrimal gland, with predominant presentation as xerostomia and dry eye. Among extraglandular manifestation of Sjogren syndrome, nonspecific manifestations like polyarthralgia and nonerosive arthritis are most common, seen in only one third of patients with primary Sjogren. Patients presenting primarily with neurological complaints, along with renal involvement, are rare, and hence, we report this case series.

Case 1

A 37-year lady presented with acute onset rapidly progressing weakness of all four limbs and associated breathlessness. She had history of hospitalization 4 months back for weakness of lower limbs, with complete recovery after 5 days of hospitalization. She could not, however, produce her medical records.

At presentation, the patient was conscious, and she had tachypnea with a respiratory rate of 42/minute. Her pulse rate was 96/minute, and the blood pressure was 120/80 mmHg. Central nervous system examination revealed hypotonia in all limbs. The power was 0/5 in both lower limbs and 2/5 in both upper limbs. Deep tendon reflexes were diminished, and plantar responses were absent. There was, however, no cranial nerve, sensory, and bowel bladder involvement. The rest of the systemic examination was grossly normal.

Within 4 hours of hospitalization, she became unconscious, oxygen saturation dropped to 85% on high flow oxygen, and the blood pressure dropped to 90 mmHg systolic. She was shifted to ICU and kept on mechanical ventilation.

Blood counts were within normal limits. Serum potassium levels were extremely low, being 1.4 mmol/L. The serum sodium, chloride, and bicarbonate levels were 143 mmol/L, 116 mmol/L, and 18.3 mmol/L, respectively. Blood gas analysis showed nonanion gap metabolic acidosis, with compensatory respiratory alkalosis. Urinary pH was alkaline (7.8). Owing to severe hypokalemia, she was given intravenous potassium correction. We were able to successfully wean her off the ventilator in next 48 hours, and she was extubated.

Further workup done for metabolic acidosis and hypokalemia included urinary osmolality, urinary potassium, sodium, and chloride levels, the reports of which were 343 mosm/kg, 7.4 mmol/L, 12.4 mmol/L, and 59 mmol/L, respectively. Anion gap in urine came out to be positive. Plasma ACTH (32 pg/ml), serum PTH (24.5 pg/ml), and ACE (28 IU/L) were all normal. Antinuclear antibody titers were positive (1:140). While she had normal anti-dsDNA titers and negative rheumatoid factor, serum SS-A/Ro (86.4 IU) and serum SS-B/La (53.6 IU) were strongly positive. Schirmer’s test showed readings less than 5 mm on strips.

Case 2

A 28-year-old lady presented with complaints of spontaneous electric shock like sensation on flexing her neck in the back region for around 2 weeks. She did not have any associated neck pain, limitation of neck movement, and dizziness. On examination, she did not have any sensory or motor weakness; however, on cerebellar examination, she had positive signs of gaze evoked nystagmus, truncal ataxia with swaying toward left, and past pointing in the left hand.

Blood counts were within normal limits. A CE-MRI Brain was done, which revealed a single irregularly T2 enhancing lesion in the left middle cerebellar peduncle, probably a demyelinating lesion [Figure 1]. The patient underwent a detailed workup with CSF studies which had albumino-cytological dissociation with positive oligoclonal bands. A VEP scan and fundus examination were also done, which were all negative. ANA by IF was positive in titers of 1:160, speckled pattern, and ENA was positive for Anti-Ro and Anti-La only. Lip biopsy showed scattered intralobular collection of plasma cells with mild fibrosis, diagnostic of Sjogren syndrome. A diagnosis of clinically isolated syndrome secondary to Sjogren syndrome was made, and the patient was managed conservatively and her symptoms subsided on its own within 2 weeks without steroids. A repeat scan was planned after a period of 1 year for dissemination of time and space; however, there were no new lesions or symptoms. The patient is doing well, asymptomatic, and under our routine follow-up.

Figure 1.

CE-MRI Brain revealed a single irregularly T2 enhancing lesion in left middle cerebellar peduncle probably a demyelinating lesion

Case 3

A 28-year-old lady presented with history of weakness in all four limbs along with difficulty in breathing; over the next 24 hours, she became drowsy. At presentation, her GCS was E2V3M1 and she was intubated in emergency. There was no history of similar illness in past. There was no associated history of fever, headache, vomiting, diarrhea, or trauma. On examination, GCS E1V1M1, neck rigidity absent, no obvious cranial nerve abnormalities, gag reflex was exaggerated, and plantars were extensors bilaterally. The patient was evaluated for acute onset altered sensorium. She was shifted to ICU on mechanical ventilation. Serum electrolytes were deranged with severe hypokalemia (2.1 mEq/l) and hyponatremia (134 mEq/L), and blood gas analysis was suggestive of nonanion gap metabolic acidosis without adequate respiratory compensation (bicarbonate 16 mEq/L, Pco2 40 mm Hg). She was started on intravenous potassium supplementation via central line along with normal saline. Further workup done for metabolic acidosis, hyponatremia, and hypokalemia included urinary pH and osmolality, urinary potassium, and sodium and chloride levels, the reports of which were 7.6 (alkaline), 332 mosm/kg, 7.1 mmol/L, 12.4 mmol/L, and 59 mmol/L, respectively. Urinary anion gap came out to be positive. Plasma ACTH (29 pg/ml), serum PTH (34.5 pg/ml), and ACE (30 IU/L) were all normal. Antinuclear antibody titers were positive (1:160). Serum SS-A/Ro and serum SS-B/La were strongly positive. The patient underwent CE-MRI Brain with spine on day2 of illness, which showed a hypointense lesion in mid pons on T1 and hyperintense lesion on T2 imaging which was suggestive of central pontine myelinolysis [Figure 2]. She was managed conservatively, however, succumbed to ventilator-associated pneumonia.

Figure 2.

CE-MRI Brain and spine showed hypointense lesion in mid pons on T1 and hyperintense lesion on T2 imaging

Case 4

A 32-year-old lady presented with complaints of numbness in hand and foot. There were also complains of progressive symmetrical thinning of the both the hand and foot. The patient presented to OPD and was examined, where there was symmetrical weakness in both hands and feet with sensory loss extending up till the knee joint and ankle, involving the touch and temperature. Nerve conducting studies were planned, which were suggestive of axonal neuropathy involving both sensory and motor neurons of all limbs. Serum ANA was done, which was positive in 1:80 titers, and ENA was positive for Anti-Ro only. The patient was started on a dose of 40 mg per day prednisone for 1 month, followed by gradual taper over 12 weeks. The patient had symptomatic improvement in 2 weeks with partial recovery of sensation in lower limbs.

Discussion

The prevalence of neurological symptoms in patients with primary Sjogren syndrome (pSS) ranges from 8.5 to 70%, the most common being peripheral neuropathy.[1] The other reported manifestations include cognitive disorders, aseptic meningitis, epileptic seizures, headache, transverse myelitis, optic neuritis, disseminated encephalopathy, and lesions in the CNS typical of multiple sclerosis.[2] The lesions in the central nervous system involve the white matter of the brain (60%) and the spinal cord (40%), mimicking multiple sclerosis (multiple sclerosis-like lesions).[3] The primary mechanism for neurological involvement in pSS is supposed to be the inflammation of the perineural vessels and perivascular inflammatory infiltration.[4]

The reported neuropathies in pSS include distal sensory polyneuropathy, axonal and demyelinating sensorimotor polyneuropathy (Guillain-Barré syndrome-like), chronic inflammatory demyelinating polyneuropathy (CIDP), multiple mononeuropathy, sensory neuronopathy, and small fiber neuropathy.[5] Concomitant renal involvement and hypokalemia secondary to distal renal tubular acidosis often complicate the diagnosis, mimicking Gullain-Barre Syndrome.[6]

In 25–60% cases, the neurological symptoms preceed the diagnosis of pSS by average 2 years.[1] In such a scenario, the diagnosis of Sjögren’s syndrome as the cause remains elusive and underrecognized, often leading to delay in specific treatment. Involvement of the nervous system in pSS is a negative prognostic factor and, usually, relates to a more aggressive course of the disease.

Conclusion

Sjogren’s syndrome has varied presentation and should be suspected in patients presenting with glandular as well as extraglandular symptoms primarily. A careful history and physical examination with serology or histopathology of minor salivary glands clinch the diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.