PD is a relatively rare neurological disorder that is less well understood by physicians in all specialties because of its atypical symptoms and normal interictal period, but is therefore easily misdiagnosed in clinical work. PKC/PKD); episodic non-motor-derived dyskinesia/episodic non-motor-derived choreoathetosis/episodic dystonic choreoathetosis (PNKD/PNKC/PDC); episodic hyperkinetic dystonia (PED), nocturnal dyskinesia (NPD/HPD), etc. The most common type of PKC is a movement-induced abnormal movement disorder with a variety of clinical manifestations, characterized by episodes of postural dystonia, hand-foot dance-like movements, and throwing-like movements.
1.Pathogenesis
PKC is a rare, exercise-induced seizure disorder with a clear family history and an autosomal dominant pattern of inheritance in most cases, with some cases being disseminated. The causative gene has been identified on chromosome 16, p11.2-q12.1, but the exact genetic nature has not been clarified. Since PKC responds well to antiepileptic drugs such as carbamazepine and phenytoin, which produce clinical effects by reducing Na ion channel activity and thus inhibiting cell membrane excitability, the genetic abnormality may be related to mutations in ion channels.
PKC patients often have a high history of infantile convulsions. Cases with a history of febrile convulsions and PKC in infancy are referred to as infantile convulsions with episodic tardive dyskinesia, which encompasses two distinct episodes, a benign infantile convulsion that occurs at 3-6 months of age and has a good prognosis for spontaneous resolution, and PKC that occurs in adolescence.
Secondary PKC is seen in intracerebral vascular lesions, traumatic brain injury, perinatal hypoxic encephalopathy and abnormal metabolic disorders such as hypoparathyroidism, hyperthyroidism, hypoglycemia, and diabetes mellitus.
2.Clinical manifestations
PKC mostly occurs in adolescence, with a male predominance and a male to female ratio of 3.75:1. The symptoms are diverse, mainly manifesting as episodes of tardive dyskinesia, postural dystonia, throwing-like movements and other involuntary movements, with clear triggers before the onset. Some patients have limb twitching and atonic seizures, mostly one-sided, and possible triggers include stress, shock, hyperventilation and continuous movement; many patients complain of “aura” before seizure, such as tingling and other sensory abnormalities, and the duration of each seizure is at least 1 to 2s and at most 5 min; the frequency of seizures can be more than 10 times a day or no seizure at all. The seizures are often unilateral, many patients are always involved ipsilaterally, some patients can be involved bilaterally, or alternately bilaterally. Speech can be affected due to the dystonia of the face or jaw. There is no impairment of consciousness during the seizure, and the interictal period is completely normal, and the seizure can be terminated by stopping or slowing down the movement.
3.Auxiliary examination
(In individual cases, EEG reveals persistent abnormal discharges in the supplementary motor areas, thus considering it as a specific kind of epilepsy). Most authors do not consider it to be epilepsy because it has no obvious brain imaging or alterations; others have found hypermetabolic basal ganglia and hypometabolic near parietal and subcortical areas on interictal SPECT in such patients. It differs from reflex epilepsy but does not exclude its epileptiform basis.
4. Diagnosis and differential diagnosis
Due to the lack of awareness of this disease, some patients have been diagnosed with hysteria, unexplained extrapyramidal disease, myopathy, and other seizure disorders.
The reasons for misdiagnosis may be due to.
(1) the low incidence of the disease and lack of awareness of the disease among clinicians.
(2) The disease is a seizure disorder with clinical features similar to epileptic-like seizures and responds well to antiepileptic drugs, so it is often misdiagnosed as epilepsy.
(3) The disease has obvious triggers and is easily misdiagnosed as a neurological disorder. It was also once thought that the pathogenesis of the disease is due to the release of postural control mechanisms from cortical control in the basal ganglia and reticular formation due to dysplastic or dysfunctional control of the neural circuits between the cortex and the basal ganglia, thalamus, and hypothalamus, speculating that it belongs to an extrapyramidal disorder.
The disease should be distinguished from several other syndromes of ictal movement disorders.
(1) episodic non-motor dyskinesia (PNKC): most of them can be triggered by alcohol, coffee, tea, ovulation, menstruation, fatigue or occur naturally, but not by sudden movements; symptoms are similar and can last from minutes to hours, but episodes are less frequent. fink et al. pointed out that its onset is related to striatal dopamine abnormalities, and treatment with levodopa and methyldopa hydrazine is effective.
(2) episodic hyperkinetic dystonia (PED): its onset is associated with prolonged or excessive exercise, such as walking and running, most often involving the movement of the feet. The pathophysiological mechanism of this syndrome is currently unknown and is largely ineffective for treatment with antiepileptic drugs.
(3) Nocturnal-onset dystonia (NPD): the presence of involuntary movements during sleep is often considered as nocturnal-onset frontal lobe epilepsy, and some authors have confirmed that it is indeed related to frontal lobe epilepsy and is homozygous for autosomal dominant inheritance of the CHRNA4 mutation in the neurogenic acetylcholine receptor gene. However, there is still no uniform understanding whether it can be identified as a seizure.
Treatment: Seizure motor dyskinesias in general respond better to antiepileptic drug therapy, especially carbamazepine and phenytoin sodium. This may be achieved by stabilizing cell membranes and blocking sodium channels. Low doses of gabapentin may also reduce the severity of seizures. bhatia has been treated ineffectively with clonidine, sodium valproate, clobazam, and valium for this disorder.
Prognosis: The course of the disease is generally nonprogressive and the prognosis is relatively good. However, some patients have increased episodes with increasing age.
In conclusion, PKC is a special kind of seizure movement disorder, which is different from seizure disorders such as epilepsy, TIA or dysthymia. Only by fully understanding its nature, early diagnosis and treatment can be achieved. It is especially necessary for integrative physicians.