Headache

A 79-year-old Caucasian female with a known history of hypertension, diabetes mellitus type 2, hypothyroidism, and mild renal impairment was admitted to our emergency department (ED) because of a sudden onset of severe bifrontal headache. The headache was rated by the patient as 8/10 on the numeric rating scale for pain. Along with that, she complained of difficulties in concentration. There were no preceding trauma and no history of migraine or other intermittent headaches. The initial neurological examination was normal. Cranial computer tomography showed minor microangiopathic and major macroangiopathic changes and strio-pallido-dentate calcifications but no other pathologies. Standard laboratory results revealed a mild microcytic hypochromic anaemia (Hb: 9,9 g/dl, MCV: 77fl, and MCH: 25pg) and a mild impaired renal function (glomerular filtration rate: 48 ml/min). Metamizole (2 g/d) was administered, which led to significant improvement and discharge.

 

Within 24 hours of being discharged, the patient experienced difficulty in speaking, and she was referred again to our ED. The neurological examination at admission still remained normal, especially with no signs of aphasia or dysarthria. Within hours, the patient became delirious with partially aggressive behaviour accompanied by optic hallucinations. Brain magnetic resonance imaging (MRI) showed minor microangiopathic changes along with small left temporoparietal postischemic defects. Moreover, bilateral strio-pallido-dentate calcifications and minor artefacts in the left occipital region related to calcification of the tentorium were noticed. A cerebrospinal fluid (CSF) analysis showed moderate lymphocytic pleocytosis (48 cells/μl; total protein: 0.695 g/l; glucose: 78.0 mg/dl; lactate: 1.8 mmol/l).

 

Broad-spectrum antimicrobial and antiviral therapy with ceftriaxone and acyclovir was initiated. The microbiological analysis of CSF showed no evidence of any bacterial or fungal pathogen. The polymerase chain reaction tests for herpes simplex 1&2 DNA, varicella-zoster DNA, cytomegalovirus DNA, Epstein–Barr virus DNA, enterovirus RNA, as well as specific anti-Borrelia burgdorferi antibodies (IgG & IgM) were negative. Nevertheless, the electroencephalography (EEG) showed no signs of epileptiform discharges or any abnormal background EEG frequencies. Even after an intravenous antimicrobial therapy for seven days, the patient's clinical state remained to a large extent unchanged. The neuropsychological screening (Montreal Cognitive Assessment: 13/30 points) showed a considerable cognitive deterioration. We decided to perform a follow-up CSF analysis to rule out the presence of paraneoplastic neuronal antibodies. Again, a moderate lymphocytic pleocytosis was observed (34 cells/μl; total protein: 0.609 g/l; glucose: 59.0 mg/dl; lactate: 1.7 mmol/l), and a serological and CSF analysis provided no signs of any pathogens. Antineuronal antibody analysis revealed normal results for anti-Hu, Ri, ANNA-3, Yo, Tr/DNER, Ma/Ta, GAD65, amphiphysin, aquaporin-4, MOG, glutamate receptors (Type NMDA and AMPA), GABA A/B receptors, LGI1, CASPR2, IgLON5, ZIC4, DPPX, anti-myelin, glycine receptors, mGluR1, mGluR5, Rho-GTPase activating protein 26, ITPR1, Homer 3, recoverin, neurochondrin, GluRD2, and flotillin ½. In conjunction to this, the CSF biomarkers for dementia showed elevated levels of tau protein (478 pg/ml, norm: <450 pg/ml) and phospho-tau protein (90 pg/ml, norm: <61 pg/ml) as well as a reduced Aß ratio (0.38, norm: >0.5). On the 10th day after hospitalization, the symptoms remained mostly unchanged, and a follow-up brain MRI was conducted. Compared to the first MRI, progressive leptomeningeal and sulcal T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities parieto-occipital on both sides and temporoparietal on the left side were seen. Moreover, increasing unspecific subcortical and periventricular T2-FLAIR hyperintensities were observed. Five days later, the patient was again referred to our ED because of the worsening of the neuropsychiatric symptoms, in particular, the visual and the auditory hallucinations. We again conducted a CSF analysis which showed no relevant changes (lymphocytic pleocytosis: 43 cells/μl; protein: 0.457 g/l; glucose: 59 mg/dl; and lactate 1.8 mmol/l; and no evidence of intrathecal IgG or IgM synthesis). Although the patient had a known history of hypothyroidism, autoimmunological laboratory diagnostic regarding thyroid antibodies was never conducted. Taking the aforementioned medical history into consideration, we augmented previous laboratory tests with autoimmune thyroid antibodies which was not done seven years ago. Here, antithyroid peroxidase antibodies (anti-TPO antibodies) were markedly increased (344 IU/l, norm: <60IU/l). Nevertheless, the thyroid-stimulating hormone (TSH), thyroxine (T4), and the triiodothyronine (T3) were within normal ranges. The ultrasound of the thyroid gland revealed no clear evidence of thyroiditis, and the patient was clinically in an euthyroid state.