Rapidly Progressive Dementia – Clinical Aspects and Management

European Neurological Review, 2011;6(4):238-245

Abstract:

Although no precise definition for rapidly progressive dementia (RPD) exists, this term is generally used to refer to cases with significant and progressive cognitive impairment that occurs over weeks or months. RPD represents an unusual but severe condition that causes distress not only for patients and their relatives but also for the clinicians involved, as multiple investigations and decisions about management must be made urgently to avoid misdiagnosing a treatable condition and to preserve as much of the neural tissue as possible from definite damage. While Creutzfeldt-Jacob disease (CJD) has for a long period of time been regarded as the prototype of RPD, this infrequent but severe condition can be produced by an extensive variety of causes such as various endocrine, metabolic or toxic disorders, central nervous system (CNS) infections, primary or secondary CNS neoplasms, various CNS vasculitides and various autoimmune conditions in which autoantibodies against neural tissue are produced, whether in the presence of a neoplasm or not. However, even in the more common and usually slowly progressive dementias such as Alzheimer’s disease, frontotemporal lobar degeneration, dementia with Lewy bodies and other degenerative dementias, as well as vascular dementia, establishment and progression of the disease is occasionally surprisingly accelerated, leading to a clinical presentation of RPD. The few published case series of RPD have shown that the relative frequency of underlying diseases depends mainly on the clinical setting. Thus, CJD has been found to be the most prevalent cause in referral centres for spongiform encephalopathies, while secondary causes are more prevalent in general referral centres for dementia diagnosis. In clinical practice, for the cases presenting with RPD, the diagnostic procedure must be exhaustive, starting with a detailed clinical evaluation and proceeding to a complete laboratory work-up and sophisticated neuroimaging studies. There has been recent enormous progress in imaging, with sensitive new sequences of magnetic resonance imaging and immunology; as a result, a plethora of antibodies against the CNS can now be detected in cases of autoimmune dementias, which has dramatically changed the diagnostic approach and early management of cases of RPD. The same favourable effect in clinical practice comes from the accumulated knowledge of the complex clinical picture of various causes of RPD, associated specific neurological features (pyramidal signs, ataxia, myoclonus) and systematic features (weight loss, hyponatraemia, hepatic disorders) and their mode of progression.
Keywords: Rapidly progressive dementia, Creutzfeldt-Jakob disease, autoimmune encephalopathies, central nervous system infections
Disclosure: The authors have no conflicts of interest to declare.
Received: October 18, 2011 Accepted November 21, 2011 Citation European Neurological Review, 2011;6(4):238-245
Correspondence: Sokratis G Papageorgiou, 2nd University Department of Neurology, ‘ATTIKON’ University General Hospital, 1 Rimini Street, Haidari, 124 62, Athens, Greece. E: sokpapa@med.uoa.gr

The term rapidly progressive dementia (RPD) is used to describe cases with a progression course which usually ranges between weeks and months.1–4 The subacute nature of RPD excludes other conditions with fulminant progression such as infectious or metabolic acute encephalopathies, which progress within hours or days and typically commence as an acute confusional state.

In most cases, the cognitive decline observed in RPD can be attributed to a single underlying disorder. Nevertheless, a rapid course might also represent the aggravation of an undiagnosed disease attributable to a secondary cause, usually an infection or a metabolic dysregulation. Various conditions involving the central nervous system (CNS) can emerge as RPD, including Creutzfeld-Jakob disease (CJD) and other spongiform encephalopathies, vascular disorders, autoimmune and paraneoplastic encephalopathies, subacute infections, metabolic and toxic disorders and systemic diseases (see Table 1). However, it is important to point out that even neurodegenerative disorders such as Alzheimer’s disease (AD), dementia with Lewy bodies and frontotemporal dementia present in rare cases as a subacute dementia instead of a slowly progressive deterioration of higher functions.5 CJD is the prevailing cause of RPD in most related studies. Regarding the relative frequency of other disorders which account for cases of RPD, there is marked variability among scientific groups.1–3 In cases of RPD with an early age of onset, the possibility of an infection, hereditary metabolic disorder or autoimmune encephalopathy should be considered.6,7

The early diagnosis of the undergoing disorder in a patient exhibiting an RPD can be particularly demanding owing to the paucity of clinical signs during the early stages of many disorders and to overlapping laboratory findings. The pattern of cognitive deficits is crucial for clinical assessment. Selective memory, executive function and language deficits might favour one potential diagnosis and exclude others. Thus, a detailed neuropsychological evaluation is crucial.2,3

The evaluation of behavioural alterations and neuropsychiatric symptoms is of high importance, since the initial symptoms can be exclusively a depressive-like or a disinhibited behaviour. Associated signs and symptoms, either neurological or systematic, can unveil an undetermined underlying disease. Ataxia, parkinsonism and specific motor or sensory deficits might herald the clinical expression of an otherwise obscure disorder during the progression of various forms of RPD.

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Keywords: Rapidly progressive dementia, Creutzfeldt-Jakob disease, autoimmune encephalopathies, central nervous system infections
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