Transient Focal Neurologic Episodes and Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) affects small arteries and arterioles of the cortex and leptomeninges. CAA is a common cause of lobar cerebral haemorrhage in elderly populations. However, recent research shows that CAA patients can also present with transient focal neurological episodes (TFNE), previously also called amyloid spells.¹

The hallmark features of TFNE are recurrent and stereotyped neurological symptoms of brief duration, typically under 30 minutes. TFNEs usually present with a spreading progression of focal motor, somatosensory, visual, or language functions.² Both positive and negative symptoms are equally common (52% vs 48%, respectively), the commonest positive symptom consisting of transient paraesthesia in the mouth or hand (32%), often but not always with a gradual spread to contiguous body parts. The negative symptoms included focal weakness and dysphasia.³

Advances in brain neuroimaging, especially MRI, allowed for further characterisation of haemorrhagic findings. TFNE’s are closely associated with convexity subarachnoid haemorrhage and cortical superficial siderosis. Cortical spreading depolarisation, also known as spreading depression, secondary to irritative blood products trapped within the cerebral sulcus is the most likely mechanism. This depolarisation propagates gradually across contiguous cortical regions, which explains the slow, smooth and somatotopic spread of neurological deficits that are a characteristic feature of TFNE’s. Nonetheless, the potential mechanism triggering cortical depolarisation remains to be demonstrated.³

Electroencephalography changes, such as intermittent focal slowing, were found in a subset of patients with TFNE, but it is not clear whether all TFNE presentations (for example, limb-jerking) can be explained by cortical spreading depression alone; seizure activity might play a role in some patients. Although there is increasing anecdotal data that antiepileptic and antimigraine medications (such as levetiracetam or topiramate) might reduce the frequency or severity of TFNE symptoms, they may also remit spontaneously. However, controlled trial data are lacking to further validate the use of antiepileptic therapy in this subset of patients.⁴

TFNE poses a common diagnostic challenge to physicians as it can be difficult to distinguish from transient ischaemic attacks or other transient neurologic syndromes such as migraine with aura, or focal seizures. Patients with TFNE are at substantial risk of subsequent lobar ICH that would be increased even further by prescription of antithrombotic medication in case of a presumed TIA. Performing MRI is therefore paramount in identifying imaging evidence of CAA when TFNE is suspected.^{1, 3}

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References:

1. Viswanathan A, Greenberg SM. Cerebral Amyloid Angiopathy in the Elderly. Ann Neurol. 2011;70:871–880.
2. Charidimou A. Cerebral amyloid angiopathy-related transient focal neurological episodes (CAA-TFNEs): A well- defined clinical-radiological syndrome. Journal of the Neurological Sciences. 2019; 406: 116496.
3. Smith EE, Charidimou A, Ayata C, Werring DJ, Greenberg SM. Cerebral amyloid angiopathy-related transient focal neurologic episodes. Neurology. 2021;97(5):231-238.
4. Banerjee G, Carare R, Cordonnier C, et al. The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice Neurol Neurosurg Psychiatry. 2017;88:982–994.