Medical Case: A student with depressive episodes, gait disorder and double vision

The symptoms cause the teenager to head into the Emergency Department. Her mother also reports depressive moods. What would you diagnose?

Depressive episodes, gait disorders and double vision: What's the cause?

Medical history: 

14-year-old patient E. S. showed up at the emergency centre, accompanied by her parents, and reported double vision and unsteady gait that had persisted for two days. The doctor noticed that the girl seemed particularly depressed and asked her mother about other abnormalities. After a short break, the mother reported, visibly worried, that her daughter had been suffering from a depressive mood for several months and had even expressed suicidal thoughts a year ago. In response, the family went on holiday, which improved the patient's mood in the short term. However, her school performance deteriorated, which is why the family is considering seeking psychological counselling.

Clinical examination:

14-year-old girl in stable general condition and obese nutritional status. Skin colour is of a rosy complexion, microcirculation unremarkable, good skin turgor, no exanthema or signs of bleeding. Diplopia in both eyes, monopedal standing and walking conspicuous, somewhat broad-based gait. Finger-to-finger and finger-to-nose tests unremarkable. No meningismus.

Laboratory and cerebrospinal fluid diagnostics:

C-reactive protein 8 mg/litre. Leukocytes: 7.28/nl. CSF: 13 cells/μl, otherwise unremarkable for glucose, lactate. Antibody analysis in CSF to follow.

Imaging:

Emergency computed tomography was used to rule out acute pathology such as haemorrhage or infarction. Magnetic resonance imaging was then performed, which showed the following pathological changes (see Figure 1 below):

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MRI findings: 

MRI examination showed marked T2w hyperintensities in the medulla oblongata, less so in the caudal pontine tegmentum, right cerebellar medulla, left posterior horn subcortical medulla, right insular/temporal medulla, around the temporal horns, right posterior cingulate and frontally on both sides. The imaging findings are consistent with limbic encephalitis.

Progression and therapy:

After the initial diagnosis, the patient was admitted to the neurological ward for further assessment. On admission, a saccadic gaze sequence, double vision and gait disturbance were also noted. Methylprednisolone shock therapy was administered over a period of 5 days. This treatment led to a slight improvement in the symptoms, in particular the saccadic gaze sequence and gait disturbance decreased.

Nevertheless, severe behavioural abnormalities continued to occur, such as reduced distance, sudden inexplicable fears and childlike behaviour. After positive NMDA receptor antibodies were detected in the cerebrospinal fluid, immunoadsorption was initiated over a total of 7 cycles. The patient subsequently developed a fever and was diagnosed with pneumonia. After antibiotic treatment, the patient's general condition improved.

During the infection-free interval, extended immunomodulatory therapy with rituximab was initiated in accordance with the guidelines. This was continued every six weeks for two years. As a result, both the psychological and neurological symptoms gradually improved.

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Figure 2: Follow-up using MRI
A: Initial imaging. B: Follow-up after 10 months. C: Follow-up after two years. There is a clear reduction in T2w hyperintensities over time, which correlates with clinical improvement.

NMDAR encephalitis, a rare and dangerous CNS disease

N-methyl-D-aspartate receptor (NMDA-R) encephalitis is an autoimmune disease characterised by the formation of antibodies against NMDA receptors in the brain. These receptors are essential components of synaptic transmission and play a central role in cognitive functions, learning and memory.

The disease was first described in 2007 and since then a deeper understanding of its clinical and pathophysiological aspects has been gained. Most patients are young women, and in many cases the disease can be associated with an ovarian teratoma, a tumour that often expresses NMDA receptors. Nevertheless, the disease can affect people of all ages and genders and can also occur without a detectable tumour.

Clinically, NMDA encephalitis often manifests with a non-specific viral prodrome, followed by psychiatric symptoms such as hallucinations, agitation, and paranoid behaviour. This phase may be followed by neurological symptoms, including impaired consciousness, movement disorders and seizures. Progression of the disease without treatment can lead to status epilepticus or coma.

Diagnosis is based on the detection of anti-NMDA receptor antibodies in serum or cerebrospinal fluid and is supported by clinical symptoms and imaging findings. Early diagnosis and treatment are crucial for the clinical course and outcome.

Therapy for NMDA encephalitis focuses on immunosuppression to reduce antibody production and control inflammation. First-line therapy often includes corticosteroids, intravenous immunoglobulin and plasmapheresis. In the event of an insufficient response, relapse or the presence of a tumour, more aggressive therapy with immunomodulators such as rituximab may be necessary.

Key take-away

As autoimmune encephalitis is usually accompanied by mental symptoms, it is often not taken seriously by non-experts. If behavioural abnormalities are detected alongside depressive moods, colleagues in medical practice and in outpatient settings should consider ruling out an organic brain cause for the mental symptoms using MRI.

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