A 56-year-Old Woman With Initial Severe Electrolyte Imbalance Who Developed Altered Mental Status,Psychosis and Catatonia

Case Presentation

A 56-year-old woman with no relevant medical history sought emergency care due to heat sensation, abdominal pain, and vomiting. These symptoms began 24 hours prior to presentation. On examination, she had dehydrated mucous membranes. Laboratory evaluation revealed profound hypovolemic hypotonic hyponatremia (serum sodium: 96 mmol/L; normal: 135-145 mmol/L), hypokalemia (2.4 mmol/L; normal: 3.5-5.1 mmol/L), hypochloremia (65 mmol/L; normal: 98-107 mmol/L), and hypocalcemia (0.99 mmol/L; normal: 1.12-1.32 mmol/L), with elevated urinary osmolarity (322 mOsm/kg), suggesting antidiuretic hormone activity. The patient denied use of diuretics or gastrointestinal losses. Neurological examination on admission was unremarkable, with no focal neurological deficits.

After admission to the intensive care unit, she received hypertonic saline. Sodium correction was targeted at ≤5 mEq/day, and this rate was maintained throughout the 2-week period. Despite electrolyte normalization after 2 weeks, new-onset neuropsychiatric symptoms emerged, including altered mental status, agitation, visual and auditory hallucinations, and psychotic behavior. Neurological examination revealed somnolence, inattention, and multiple signs of catatonia: negativism, mutism, catalepsy, rigidity, fixed gaze, and a right palmo-mental reflex. These symptoms progressed over several days and significantly impaired her ability to communicate and interact with her surroundings. She was disoriented, exhibited flattened affect, and showed profound withdrawal. A psychiatric evaluation ruled out primary psychiatric illness, reinforcing the suspicion of an underlying organic encephalopathy

Clinical Reasoning and Diagnostic Workup

This patient initially presented with gastrointestinal symptoms and profound electrolyte disturbances, most notably severe hyponatremia. Following correction, neurological and psychiatric symptoms developed, including psychosis and catatonia. Although the correction rate was within safe limits, osmotic demyelination syndrome was a key differential and was ruled out by brain MRI, which showed no structural lesions.

Given the emergence of acute cognitive changes, psychosis, and catatonia, autoimmune encephalitis was considered, guided by the diagnostic framework established by Graus et al, ¹ which emphasizes a syndrome-based approach for early identification. This approach relies on clinical features such as subacute onset of altered mental status, psychiatric symptoms, and exclusion of alternative diagnoses, even in the absence of autoantibody confirmation. Based on these criteria, our patient met the requirements for a diagnosis of ‘possible autoimmune encephalitis’, given her subacute presentation of new-onset neuropsychiatric symptoms, catatonia, and absence of an alternative diagnosis despite extensive metabolic, infectious, and structural evaluation. The Bush–Francis Catatonia Rating Scale, a tool designed to identify and measure the severity of catatonic signs, was used to assess the patient. The 14-item screening tool detects catatonia when at least 2 signs are present, while the full 23-item scale rates symptom severity. Key features include mutism, posturing, rigidity, and echophenomena—comprising echolalia (the repetition of another person’s spoken words) and echopraxia (the imitation of another person’s movements or gestures). ² A standardized 5-minute examination was conducted daily. Following the identification of catatonia, a lorazepam challenge was administered, with subsequent improvement in clinical signs. A positive lorazepam challenge is defined as the resolution or significant improvement of catatonic features within 5 to 10 minutes after intravenous administration of 1-2 mg of lorazepam, thereby supporting the diagnosis of catatonia and the use of benzodiazepines as first-line therapy. ² This response to benzodiazepines supported the diagnosis and guided ongoing management. Although there was no fever or meningismus, the prior report of heat sensation prompted lumbar puncture. CSF (cerebrospinal fluid) analysis showed 1 WBC, glucose 50 mg/dL, protein 66.9 mg/dL, and a CSF/serum glucose index of 0.58. Viral and bacterial PCRs included in the multiplex meningitis/encephalitis panel were negative. The panel included: herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, human herpesvirus 6, enterovirus, parechovirus, Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae, Streptococcus pneumoniae, and Cryptococcus neoformans/gattii. Bacterial and fungal stains and cultures were also negative.

Electroencephalogram (EEG) showed mild generalized dysfunction without epileptiform activity. The EEG findings of mild generalized dysfunction, though non-specific, further supported the presence of a diffuse cerebral process consistent with autoimmune encephalitis. ¹ Transcranial Doppler ultrasound revealed no signs of vasculitis. However, transcranial Doppler has limited sensitivity for detecting small- and medium-vessel vasculitis and cannot definitively exclude central nervous system (CNS). Serum onconeural (intracellular antigen) antibody panel results were negative. Additionally, surface neuronal antibodies in both CSF and serum were tested and found to be negative, further supporting the diagnosis of antibody-negative autoimmune encephalitis. A PET-CT was performed due to the absence of diagnostic findings on conventional imaging and CSF analysis, combined with the high clinical suspicion for autoimmune encephalitis. This imaging revealed global cortical hypometabolism and increased metabolic activity in the right submandibular gland (Figure 1).OPEN IN VIEWER

The initial electrolyte imbalance was presumed to be renal in origin, with FENa 2.38%, urinary sodium 89 mEq/L, and urinary chloride 89.8 mmol/L. Severe hypokalemia (UK:Cr = 39.9, TTKG = 16) with normal magnesium suggested a renal tubulopathy.

Although sicca symptoms were not initially reported, further interviews with family members revealed xerophthalmia, xerostomia, and polyarthralgia. An autoimmune panel showed markedly elevated anti-SSA (25 282 U) and anti-SSB (9441 U) antibodies. A biopsy of the right submandibular gland showed lymphoplasmacytic infiltration, fibrosis, and acinar atrophy (Figure 2).OPEN IN VIEWER

Diagnosis of primary Sjögren’s Syndrome (pSS) was established based on the 2016 ACR/EULAR classification criteria, with a total of 6 points: 3 for positive anti-SSA antibodies and 3 for biopsy-proven lymphocytic infiltration (≥4 points = diagnosis; sensitivity 96%, specificity 95%). ³ In addition to CNS and renal involvement, the patient developed generalized pruritic dermal lesions, and skin biopsy confirmed leukocytoclastic vasculitis.

Treatment and Outcome

Treatment began with methylprednisolone 1 g/day for 5 days, resulting in rapid clinical improvement and resolution of psychiatric symptoms. She then received 5 doses of intravenous immunoglobulin (IVIG), followed by rituximab. Her EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score at presentation was 33, indicating high disease activity, and declined to 2 points by discharge. ³ The patient returned to her baseline mental and physical function and resumed daily activities.

Discussion

Evaluation of non-infectious encephalitis requires a systematic approach. According to the proposed criteria by Graus et al., ¹ the diagnostic workup should begin with clinical suspicion based on subacute onset of neuropsychiatric symptoms, including behavioral changes, altered consciousness, or cognitive decline. Initial testing should include contrast-enhanced brain MRI to identify inflammatory or structural changes, cerebrospinal fluid (CSF) analysis to evaluate for pleocytosis, elevated protein, or oligoclonal bands, and serologic screening for autoimmune markers or paraneoplastic antibodies. EEG may support the presence of encephalopathy but is not specific. ¹

When these studies are inconclusive and clinical suspicion persists, 18F-FDG PET-CT should be considered. This imaging modality has demonstrated higher sensitivity than MRI in detecting metabolic abnormalities, particularly in cases of limbic encephalitis where MRI findings are negative or non-specific. PET-CT frequently shows medial temporal hypermetabolism and may also reveal extra-limbic abnormalities such as in the brainstem or cerebellum, which correlate with clinical severity and disease activity. It has also been valuable in antibody-negative autoimmune encephalitis and may help in subclassifying these syndromes. Moreover, whole-body PET imaging can concurrently assess for paraneoplastic sources, supporting its inclusion in the diagnostic algorithm when autoimmune encephalitis is suspected.^4,5

Autoimmune encephalitis in the context of an underlying systemic autoimmune disease such as pSS poses significant diagnostic challenges, particularly when classic sicca symptoms are absent. In this patient, initial workup — including MRI, CSF analysis, and EEG — was unremarkable, leading to diagnostic uncertainty. The use of 18F-FDG PET-CT, which revealed diffuse cortical hypometabolism and increased uptake in the submandibular gland, played a pivotal role in redirecting clinical suspicion toward an autoimmune etiology. These findings prompted targeted serologic testing and glandular biopsy, ultimately confirming the diagnosis of pSS. Notably, in a case review of 18 patients with pSS, 72% presented with acute encephalitis as their initial manifestation, underscoring the need to consider this diagnosis even in the absence of classic features. ⁶

Importantly, autoimmune encephalitis may occur without detectable antibodies or overt systemic signs, making it essential to maintain a broad differential diagnosis and to incorporate functional imaging when conventional evaluations are inconclusive. Beyond encephalopathy, pSS is known to present with a diverse array of CNS manifestations, including depression, memory loss, cognitive impairment, focal demyelinating lesions, aseptic meningitis, cerebellar syndromes, neuromyelitis optica, and movement disorders. The pathogenesis is believed to involve immune-mediated brain dysfunction, highlighting the importance of timely recognition and intervention. ⁶

The patient met the 2016 ACR/EULAR classification criteria pSS, with a total of 6 points: 3 points for positive anti-SSA/Ro antibodies and 3 points for labial salivary gland biopsy demonstrating focal lymphocytic sialadenitis with a focus score ≥1 focus/4 mm². ⁷ These findings, together with sicca symptoms and systemic involvement, confirmed the diagnosis. ³

Extraglandular manifestations included CNS involvement with encephalopathy, psychosis, and catatonia ⁹ ; renal tubular dysfunction with severe electrolyte imbalances; and cutaneous vasculitis. These features, though less common, are recognized in pSS.^8,10,11,12 Distal renal tubular acidosis may occur in up to 70% of cases. ¹²

Systemic disease activity was quantified using the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), with an initial total score of 33 points, reflecting high disease activity. This score was composed of 13 points in the CNS domain, 6 in the renal domain, 5 in the cutaneous domain, 4 in the biological domain (due to elevated antibody titers), 3 in the constitutional domain, and 2 in the articular domain. ¹³ Treatment included high-dose methylprednisolone, IVIG, and rituximab, resulting in marked clinical improvement. The final ESSDAI score decreased to 2 points, consistent with low disease activity, and the patient returned to her baseline mental and functional status.

There are no solid evidence-based guidelines for treating each neurological manifestation in pSS. Peripheral neuropathies are typically managed with oral corticosteroids and immunosuppressants, while CNS alterations may necessitate high-dose steroids, rituximab, plasmapheresis, immunoglobulin, azathioprine, methotrexate, or mycophenolate mofetil, depending on severity. In the presented case, significant improvement was observed with early steroid doses, IVIG, and rituximab, consistent with previous studies.^3,6,8

This case contributes a rare and instructive example of pSS with CNS involvement, notably presenting with encephalopathy, psychosis, catatonia, renal tubulopathy, and small vessel vasculitis. While neurologic manifestations of pSS are uncommon, their occurrence as the initial or dominant presentation — particularly in the absence of sicca symptoms — presents a significant diagnostic challenge. The absence of similar reports from the Mexican population underscores the relevance of this case to the broader understanding of regional and phenotypic variability. Its diagnostic trajectory reinforces the importance of maintaining a broad differential in patients with cryptogenic encephalopathy and multisystem features.

In such scenarios, early autoimmune screening, use of metabolic imaging such as 18F-FDG PET-CT, and prompt initiation of immunomodulatory therapy may be critical to achieving neurologic recovery. This case highlights the need for heightened clinical suspicion of autoimmune etiologies, even when conventional criteria are not initially met, and demonstrates how timely, targeted interventions can lead to meaningful recovery in complex multisystem disease.