Case 27 – Rapidly Progressive Behavioral Changes and Cognitive Symptoms in a 29-Year-Old Woman

Abstract

A 29-year-old woman was referred to a community hospital. She was accompanied by her parents. They reported that behavioral and personality changes had been present for 3 days. The patient suddenly had started to speak almost incomprehensibly. She also had become obtrusive and impulsive. In addition, she had talked to imaginary people and introduced herself as another person. The physicians at the hospital described her as an aggressive person with incoherent thinking, pathological crying, and hallucinations. No focal neurological signs were observed. With suspected schizophrenic psychosis, the patient was transferred to a psychiatric department.

Case 27 Rapidly Progressive Behavioral Changes and Cognitive Symptoms in a 29-Year-Old Woman

Peter Hermann , Katharina Hein , Katrin Radenbach , and Inga Zerr

27.1 Case Report

27.1.1 Onset and Early Clinical Course

Because of rapidly progressive symptoms, fluctuating vigilance, and mild leukocytosis in the blood, the patient was sent back to the casualty department the next day. A cerebral CT-scan showed no pathological results. A lumbar puncture was performed and the analysis of the cerebrospinal fluid (CSF) revealed elevated leukocyte count (36/µL). The patient was transferred to a general intensive care unit and received aciclovir 2,250 mg/d and ceftriaxon 2 g/d to treat the suspected infection of the central nervous system and haloperidol and diazepam because of the hallucinations and agitation. Another 2 days later, she was transferred to the neurological intensive care unit of a university hospital for further diagnosis and treatment.

27.1.2 Patient’s Medical History

The patient had no personal or family history for psychiatric disorders. She did not misuse alcohol or illegal drugs. Before onset, she received no medication and no allergies or chronic internal diseases were present. She had normal intelligence and worked as an electronic technician until 3 days before onset of clinical symptoms. At the age of 13, she underwent a partial resection of the right ovary. Histopathological reports described a differentiated cystic teratoma (dermoid cyst), which showed no signs of malignity.

27.1.3 Imaging, EEG, and CSF-Analysis

A computed tomography (CT) scan 4 days after clinical onset showed no pathological results. The first cerebral magnetic resonance imaging (MRI) was performed 7 days after onset. Neuroradiologists described suspicious but not unambiguous signal hyperintensities of both hippocampi on fluid-attenuated inversion recovery (FLAIR)-weighted images (see Figure 27.1).

Figure 27.1 On T1 and DWI, no abnormalities and no pathological enhancement of contrast agent could be observed. Later MR-images showed the same results.

Several electroencephalographies (EEG) were performed during acute treatment but showed no distinct epileptiform activity. Depending on sedative medication, either massive movement artifacts or general slowing of normal rhythm were recorded. Later EEG showed rhythmic focal delta activity in frontal and temporal regions on both hemispheres.

The first lumbal puncture was performed 4 days after onset. Within a narrow time frame, an elevation of leucocytes (36/µL) as well as normal CSF proteins (430 mg/L), albumin ratio (4.9), lactate (1.8 mmol/L), and glucose could be measured. Because of the detection of intrathecal synthesis of IgG and pleocytosis, diagnosis of an inflammatory process of the brain was made. Specific antibodies against human herpes virus (HHV) 1-3, measles virus, rubella virus, Epstein–Barr virus, cytomegalovirus, and Borrelia were normal. Within 3 days after lumbar puncture, results from polymerase chain reaction (PCR) (HHV 1-3: negative) and detection of further antibodies were available. Paraneoplastic antibodies (e.g., GAD65, Ma1, Ma2, amphiphysin, Ri, Yo, HuD) were not detectable. Immunofluorescence for neuronal antibodies like CASPAR2, AMPAR1, AMPAR2, LGI1, and DPPX was negative but NMDA-receptor antibodies showed up clearly positive.

With history of ovarian teratoma in mind, abdominal imaging was performed. CT and MRI showed polycystic ovaries on both sides. Sonographically, a dermoid cyst of the right ovary was suspected.

27.1.4 Case Management and Further Course of Disease

When the patient had arrived at a specialized neurological intensive care unit, she was soporous. In addition, an acute renal failure with increased serum creatinine and decreased glomerual filtration rate was diagnosed. The differential diagnosis of the reduced vigilance might have been caused by a combination of sedative and antipsychotic medication, possible nonconvulsive seizures, or as direct consequence of encephalopathy or encephalitis. Antipsychotic medication was reduced and antiepileptic therapy with valproic acid was started, although the EEG showed no distinct epileptiform activity. The acute renal failure was most likely induced by previously started acyclovir therapy. Because of negative HHV-PCR, absence of bacterial growth in CSF cultures and history of ovarian teratoma, physicians suspected an autoimmune encephalitis. Then antiviral therapy was discontinued. In the further course, renal function recovered. Intravenous therapy with methylprednisolone (1 g/d) had already been induced 1 day before the patient was relocated. This therapy continued for overall 5 days. Meanwhile, the positive result for NMDA-receptor antibodies was available and plasmapheresis was planned. The patient had received three cycles, when a pneumonia occurred and had to be treated. Although abdominal CT and MRI showed no obvious results, recurrence of a right ovarian dermoid cyst was suspected sonographically. Plasmapheresis was discontinued for 1 week and the patient underwent a laparoscopic adnexectomy on the right side. Histopathological results showed a differentiated ovarian teratoma without signs of malignity. Plasmapheresis was continued for another four cycles. The patient became more vigilant and showed less severe psychiatric symptoms. Oral medication with prednisolone was started. In follow-up CSF analysis, leucocyte count was decreasing.

The patient was discharged from intensive care unit and transferred to neurologic rehabilitation after 5 weeks of treatment. At this point, she was vigilant but still suffered from cognitive problems, especially severe memory deficits and psychomotor impairment. No major psychotic symptoms were present, but she still received haloperidol. During neurologic rehabilitation, an episode with agitation and hallucinations occurred and continued for 3 days. Antipsychotic medication was switched to olanzapine and the patient was transferred to a psychiatric ward, where no more aggressive behavior or psychotic symptoms were observed. However, cognitive deficits and depressive mood were still present. Medication with antidepressants was started and the patient could be relocated to complete neurological rehabilitation. Eight weeks after onset, the patient underwent another lumbar puncture as follow-up examination. As leucocyte count was normal and intrathecal IgG synthesis was not detectable anymore, slow reduction of prednisolone and valproic acid was started. However, NMDA-receptor antibody immunofluorescence was still slightly positive. Temporary reduction of olanzapine led to delusional mood without hallucination or agitation. Eight months after disease onset and after further outpatient treatment, the patient showed isolated moderate episodic memory deficits. Antipsychotic medication had been ceased. The patient still received lamotrigine and 7.5 mg prednisolone. For an overview, see Table 27.1, which summarizes CSF results, clinical symptoms, and most important therapeutic measures over a period of 8 months.