Rapidly Progressing Dementia – Clinical Aspects and Management
common cause of limbic encephalopathy and is usually associated with small-cell lung cancer. Other neurological manifestations include myelitis, non-convulsive status epilepticus and peripheral sensory neuropathy.54
Figure 3: A Patient Diagnosed with Limbic Encephalitis
Anti-CV2 antibodies (anti-CRMP5) can be observed in cases of small-cell lung cancer and thymoma. Cerebellar degeneration, myelitis, chorea, optic neuropathy and sensory neuropathy may occur as well. Anti-Ma2 antibody is associated with testis germ cell tumours, small-cell lung cancer and breast cancer and, in addition to limbic encephalopathy, affected patients may also present limb rigidity, vertical gaze palsy, sleep abnormalities and orafacial dystonia.52,53
Paraneoplastic encephalitis with N-methyl D-aspartate receptor antibodies occurs in young women with an underlying ovarian teratoma. Memory problems are often combined with psychiatric symptoms, dyskinesias and alterations of the level of consciousness. MRI may reveal an increased signal in the cerebral and cerebellar cortex in FLAIR sequence.55
Patients often exhibit signs of limbic encephalitis, occasionally combined with neuromuscular hyperexcitability. Brain MRI may reveal an increased signal in the mesial temporal lobe. Morvan syndrome includes acquired neuromyotonia, dysautonomia, myokymia, insomnia and encephalopathy with hallucinations and fluctuating cognition. Diagnosis can be confirmed by means of needle electromyography showing spontaneous muscle activity. The disorder exhibits a quick response to corticosteroid treatment or plasma exchange therapy.52,57
Antibodies against neuronal VGKC may be related to lung cancer or thymoma, but most cases are not paraneoplastic, especially in the absence of other paraneoplastic autoantibodies. VGKC autoantibodies have been correlated with acquired neuromyotonia (Isaac’s syndrome).56
Antiglutamic acid decarboxylase (anti-GAD) antibodies can be observed in various conditions including type 1 diabetes and stiff person syndrome. Occasionally, the presence of anti-GAD antibodies may herald the development of a subacute encephalitis with RDP, ataxia, autonomic instability, myoclonus and trunk rigidity responding to immunosuppressive therapy.58
Autoimmune encephalopathies with rapid progression can mimic CJD in terms of clinical and MRI findings. The latter is particularly true for limbic encephalopathy, with anti-VGKC antibodies exhibiting cortical ribonning.59 The laboratory investigation for antineuronal autoantibodies (anti-Hu, anti-Ma, anti-CV2 and anti-VGKC) is therefore of high importance. In selected cases, computed tomography of the thorax and abdomen and whole-body positron emission tomography may reveal an underlying tumour such as an early-stage small-cell lung carcinoma.4,52
Hashimoto Encephalopathy
Hashimoto thyroiditis has been implicated in the development of neurological and psychiatric symptoms. Its most severe clinical expression affecting brain function is Hashimoto encephalopathy, a steroid-responsive encephalopathy associated with high titres of serum antithyroid antibodies.60,61
The disorder mainly affects
middle-aged women. The patient may be euthyroid, hypothyroid or even hyperthyroid, although a return to a euthyroid status is essential to establish the diagnosis. The encephalopathy course is either that of stroke-like relapsing–remitting episodes or that of a progressive cognitive impairment. Myoclonus, generalised seizures, sleep disturbance and psychiatric symptoms, namely visual hallucinations,
EUROPEAN NEUROLOGICAL REVIEW Brain magnetic resonance imaging shows non-enhancing signal changes in the hippocampi.
might also be present. Laboratory findings include abnormal EEG, elevated CSF protein and elevated serum antithyroid antibodies (anti-thyreoglobulin antibodies [anti-TG] and anti-thyroid peroxidase antibodies [anti-TPO], the latter being more common). However, these markers are not disease-specific and may also be present in other autoimmune disorders. MRI might be normal or present subtle, non-specific findings such as white matter hyperintense lesions (see Figure 4).62–64
Hashimoto
The EEG will show non-specific slowing and occasionally epileptiform discharges suggestive of CJD.65
encephalopathy responds well to corticosteroid treatment, which can be prolonged to achieve a full remission.
Other Autoimmune Conditions
Systemic autoimmune disorders such as systematic lupus erythematosus and Sjogren’s syndrome can manifest as a rapidly progressive dementia in rare cases. Systemic lups erythematosus affects the CNS in almost 75 % of cases either by means of antibodies against the CNS parenchyma or indirectly, causing an antibody-mediated vasculitis.66
Common CNS findings include
cognitive impairment, psychiatric disorders, seizures and stroke episodes. The presence of antiphospholipid antibodies may contribute to this situation. Transverse myelitis and peripheral neuropathy may also be observed during the course of the disease. Despite the fact that Sjogren’s syndrome often involves the peripheral nervous system (sensory neuropathy), it can also affect the CNS. On rare occasions it can present as an RPD with cognitive decline and mood disorders. Nevertheless, the most common CNS symptoms of Sjogren’s syndrome are recurrent attacks with focal symptoms mimicking multiple sclerosis. Primary or secondary vasculitis of the CNS, such as polyarteritis nodosa or Wegener’s granulomatosis, can cause an encephalopathy resembling RPD. Detection of perinuclear and cytoplasmic antineutrophil cytoplasmic antibodies (in secondary vasculitis), brain CSF inflammation findings, MRI data (ischaemic lesions, leukoencephalopathy and gadolinium enhancement of the meninges) may facilitate the diagnosis, which is confirmed by means of angiography.
Coeliac disease occasionally presents with cognitive decline, psychiatric symptoms, ataxia, seizures, neuropathy and headaches independently of systematic symptoms (malabsorptive syndrome). Progression of
243
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68