Introduction

Micrographia, the reduction in handwriting size, is one of the characteristic symptoms of parkinsonism. In general, micrographia is unique to parkinsonism. This complication is rarely seen in patients with disorders other than neurodegenerative disorders such as Parkinson disease and cerebrovascular disorders such as vascular parkinsonism. A few cases with cerebral angiitis syndromes, such as systemic lupus erythematosus, Sjogren’s syndrome and more rarely, rheumatoid arthritis have been reported [1]. In these cases with angiitis, basal ganglia are often the targets of the lesions. Although numerous studies in recent years have revealed various kinds of neurological complications in steroid-responsive encephalopathy associated with antibodies to thyroid peroxidase, i.e., Hashimoto encephalopathy (HE) [2], there has been no report in which parkinsonian gait is described. One of the reasons for this is that it is difficult to distinguish parkinsonism from consciousness disturbance, although many patients present with gait disturbance. We describe for the first time a rare case of gait disturbance and micrographia as a typical feature of parkinsonism.

Case report

The patient was a 63-year-old woman who presented with parkinsonian gait with micrographia. The patient had no familial history of neurological disorders. Ten months before admission, her neurological symptoms appeared and progressed gradually. At the same time, she noticed edema and arthralgia in the extremities of unknown etiology. Edema palliated gradually within 1 month and arthralgia in her ankles was alleviated within another month. Two months before admission, she noted difficulty and slowness in writing. Subsequently, she developed gait disturbance. No dryness of eyes or mouth was presented. On admission, neurological examinations revealed abnormal postural reflex and parkinsonian small-stepped gait. Cognitive functions and intellectual performance were normal, though the patient sometimes showed drowsiness and could only provide correct answers for up to four digits in the digit span test. She spoke in a small monotonous voice. Postural finger and jaw horizontal tremors were noted bilaterally. Finger tremor was reduced in a resting position. When she wrote, slowness and micrographia were recognized (Fig. 1). Ocular movement was full and smooth, and without nystagmus. Deep tendon reflexes were normal and there was no pathological reflex. Muscle tonus of the neck and extremities was normal. No apparent paresis, abnormal sensations including deep sensations or autonomic dysfunctions were found.

Fig. 1
figure 1

a The patient’s handwriting of a dinner menu 4 days before the start of seteroid therapy. Note the numbers 19, 20 and 21, which indicate the 19th, 20th and 21st days of the month. The handwriting started to become clumsy on the 19th day and this indicated micrographia (two dotted lines show decrescendo) on the 21st day. b The patient’s normal handwriting after steroid therapy. Note the numbers 28 and 29, which indicate the 28th and 29th days of the month

Full size image

Laboratory data revealed various immunological abnormalities and low vitamin B12 level (201 pg/ml, normal range 233–9140 pg/ml). Although the results of a thyroid function test were normal, anti-thyroid peroxidase antibodies were elevated (19.5 U/ml, normal range <0.29 U/ml). Anti-thyroglobin IgG was positive (100×, normal range <99.9×). Interleukin-2 receptors, anti-parietal cell antibody, and rheumatoid factors with anti-galactose-deficient IgG antibody were also elevated. No serum SS-a or SS-b antibody was elevated. Anti-VGKC, anti-NMDA-GluRε2 receptor and anti-NMDA-GluR δ2 antibodies were not elevated. Anti-NAE autoantibodies in the serum, a diagnostic marker for HE, were strongly positive [3]. Magnetic resonance imaging of the brain was almost normal except for scattered ischemic-like changes in the brain white matter. Cerebrospinal fluid (CSF) showed mononucleocytosis (552/μl, 447 lymphocytes and five polynucleocytes) with elevated protein levels (164 mg/dl, normal range <49 mg/dl). Upper gastrointestinal fiberscopic examination revealed atrophic gastritis. Electroencephalography (EEG) revealed slowness of background activity, which was normalized 1 month after the start of steroid therapy. After admission to our hospital, methyl prednisolone pulse therapy (1 g/day) was performed for 3 days. Her neurological symptoms began to improve 2 days after the start of therapy. Oral administration of prednisolone at the dose of 15 mg was followed by steroid pulse therapy. 2 weeks later, her symptoms had completely disappeared. Since tapering off the steroid, no relapse has occurred for 3 years.

Discussion

HE was first reported as an autoimmune neuropsychiatric condition associated with thyroid disorders such as Hashimoto’s thyroiditis [4]. The main features of HE are altered consciousness, impaired attention and cognition, and associated changes in behavior (agitation or lethargy) and personality [2]. Therefore, the presentation of parkinsonism as the main symptoms was unique for HE. The diagnosis of HE was supported by the results of laboratory and radiological examinations including elevated protein with mild lymphocytic pleocytosis in CSF, presence of anti-TPO antibodies and anti-NAE autoantibodies, slow background activity in EEG and normal appearance on brain MRI except for scattered white matter lesions as described elsewhere [2, 4]. Furthermore, the patient showed excellent response to steroid treatment. Autoantibodies against α-enolase have been reported in sera of HE patients, and its NH2 terminal region was shown to be specific for HE [3, 5, 6].

The patient also had other immunological abnormalities such as high levels of interleukin receptor II, anti-parietal cell antibody and rheumatoid factor with anti-galactose-deficient IgG antibody. It has been reported that about 30% of patients with autoimmune thyroid disease have vitamin B12 deficiency due to type A gastritis, which is caused by anti-parietal cell antibody [7].

Although the pathological mechanism of HE is still unknown, vasculitis might be a cause. Alpha-enolase serves as a plasminogen receptor on the surface of a variety of hematopoetic, epithelial and endothelial cells, which may have a role in intravascular and pericellular fibrinolytic systems [8]. In fact, vasculitis was reported in an autopsy case of HE [9]. In systemic vasculitis, renal failure accompanying pitting edema, arthralgia and pulmonary hypertension have been reported [1]. Women with glomerulonephritis had a significantly greater prevalence of anti-TPO antibodies (odds ratio 3.85, 95% confidence interval 1.04–14.3) [10]. In fact, our patient had an episode of transient pitting edema due to mild renal insufficiency with ankle arthralgia. These features are suggestive of the existence of systemic vasculitis in our patient.

Since most HE patients experience consciousness disturbance [2], the consciousness impairment conceals neurological manifestations such as parkinsonism. Therefore, although gait disturbance has already been reported in HE cases [2], it is still not clear whether gait disturbance is due to parkinsonism or just consciousness disturbance. Presentation of micrographia, which is typical feature of parkinsonism, in our patient suggested that HE could have impaired the function of basal ganglia at the initial stage, thus demonstrating parkinsonism.

This report suggests that our patient with progressive micrographia and parkinsonian gait warrants a diagnosis of HE. HE should be considered in differential diagnosis of parkinsonism in patients who do not show significant consciousness impairment, especially in patients who show various immunological abnormal manifestations and who have received steroid therapy before the symptoms become permanent.