Diagnostic and therapeutic aspects of Hashimoto's encephalopathy

https://doi.org/10.1016/j.jns.2013.05.009Get rights and content

Abstract

Objective

To share our experience on clinical presentation and management of patients diagnosed with Hashimoto's Encephalopathy (HE) at Vanderbilt Medical Center between 1999 and 2012.

Background

HE is a rare disorder characterized by encephalopathy and central nervous system (CNS) dysfunction, elevated antithyroid antibodies, the absence of infection or structural abnormalities in the CNS, and a response to treatment with steroids. The relationship between thyroid antibodies and encephalopathy has remained unresolved.

Design/Methods

Retrospective chart review.

Results

We identified 13 patients who met the criteria for the diagnosis of HE. The median age was 49 years (range, 2–66) and all except one were women. Encephalopathy in the form of altered mental status, stroke-like symptoms or seizures, with prompt resolution of symptoms upon receiving steroids, was the commonest presentation, seen in 7 patients. The second commonest presentation was subacute progressive decrease in cognitive function, which reversed within days to weeks after steroid therapy, seen in 4 patients. Electroencephalogram (EEG) was available in 12 patients and was abnormal in 8, showing nonspecific cerebral dysfunction in all 8 and epileptiform activity in 3. Treatment consisted of steroids in the acute phase for 12 of 13 patients with rapid improvement in symptoms. Maintenance therapy was rituximab in 7 patients, intravenous immunoglobulin (IVIg) in 7, azathioprine in 4, mycophenolate mofetil in 3, and methotrexate in 1 (some patients received sequential therapy with different agents). There was complete or near complete resolution of symptoms in 12 of the 13 patients.

Conclusions

We present a cohort of patients in whom CNS dysfunction was associated with elevated antithyroid antibodies and reversal of disease followed immunomodulatory therapies.

Introduction

HE is characterized by encephalopathy and elevated anti-thyroid antibodies in the absence of a central nervous system infection, tumor or stroke [1], [2]. It is a rare disorder with an estimated prevalence of 2/100,000 [3] but is treatable, making it an important consideration in the approach to patients presenting with subacute encephalopathy.

The first report of HE in 1966 described a 49 year old man with hypothyroidism, on therapy with thyroxine, developing hallucinations, tremor, agitation, followed by altered mental status (AMS) [4]. It has since been recognized that the presentation of HE is extremely varied, ranging from a fulminant encephalopathy to a chronic dementia [5]. Reported presentations of HE include amnestic syndrome [6], seizures including status epilepticus [7], focal neurological deficits such as ataxia [8], [9], [10], [11] and myoclonus [12], [13], and psychiatric manifestations including depression [14], mania [15], psychosis and hallucinations [16], [17], [18].

Steroids are the first line treatment in HE [19], but patients may relapse as the steroids are tapered, necessitating the use of other therapies to avoid the long-term adverse effects of steroids. However while plasmapheresis [20], [21], [22] and intravenous immunoglobulin (IVIg) [23], [24] have been reported to be of benefit, there are few reports of long-term outcomes associated with immunomodulatory therapies in HE.

We examined the presentation of patients with HE seen at Vanderbilt Medical Center between 1999 and 2012. As noted above, the clinical presentation of HE is highly variable and here we report features that are associated with this clinical syndrome and should raise consideration for the diagnosis of HE. We have also managed our HE patients on long-term azathioprine, mycophenolate mofetil and rituximab, which have not been reported in the literature until now. We believe that sharing our experience will help physicians especially with long-term management of HE cases.

Section snippets

Methods

We defined the following criteria for the diagnosis of HE: (a) acute or subacute onset of altered mental status, (b) elevated antithyroid antibodies (c) rapid response in mental status with corticosteroids and (d) absence of structural, infectious or other metabolic factors which could explain the AMS and its response to steroids. After obtaining approval from the Vanderbilt IRB, a database of 6100 patients treated at the Vanderbilt Multiple Sclerosis Clinic between 1995 and 2012 was searched

Clinical presentations in HE

The median age was 49 years (range, 2–66) and 12 of the 13 patients were women. Encephalopathy in the form of altered mental status, stroke-like symptoms or seizures, with prompt resolution of symptoms upon receiving steroids, was the commonest presentation, seen in patients 1, 2, 3, 5, 6, 7 and 8. A subacute progressive decline in cognitive function, which reversed within days to weeks after steroid therapy, was the presenting feature in patients 9, 10, 11 and 12. Three patients had other

Discussion

The diagnosis of HE can be fairly straightforward when patients with no prior neurological problems present with a well-defined encephalopathy (Table 1). Subacute, progressive cognitive decline (patients 9, 10, 11 and 12, Table 1) has a large differential diagnosis [25]. The diagnosis of HE in these patients was made after MRI, and laboratory studies including CSF studies revealed no other cause, anti-thyroid antibodies were elevated, and the cognitive decline reversed after steroid therapy. A

References (35)

  • D.J. McCabe et al.

    Amnesic syndrome with bilateral mesial temporal lobe involvement in Hashimoto's encephalopathy

    Neurology

    (2000)
  • J. McGinley et al.

    Hashimoto's encephalopathy; an unusual cause of status epilepticus

    Ir Med J

    (2000)
  • A. Matsunaga et al.

    Hashimoto's encephalopathy as a treatable adult-onset cerebellar ataxia mimicking spinocerebellar degeneration

    Eur Neurol

    (2012)
  • H. Nakagawa et al.

    Hashimoto's encephalopathy presenting with progressive cerebellar ataxia

    J Neurol Neurosurg Psychiatry

    (2007)
  • H. Nakagawa et al.

    Hashimoto encephalopathy presenting with progressive cerebellar ataxia

    BMJ Case Rep

    (2009)
  • Y. Tang et al.

    Hashimoto's encephalopathy mimicking spinocerebellar ataxia

    J Neurol

    (2011)
  • K. Gucuyener et al.

    Tremor and myoclonus heralding Hashimoto's encephalopathy

    J Pediatr Endocrinol Metab

    (2000)
  • Cited by (91)

    • Rare autoimmune and autoinflammatory neurologic disorders

      2023, Translational Neuroimmunology: Neuroinflammation: Volume 7
    View all citing articles on Scopus

    Financial Disclosures: The authors have no financial relationships relevant to this article to disclose and they have no conflict of interest.

    View full text