Dejerine-Roussy Syndrome

Etiology

Any vascular lesion or disease involving the central somatosensory system carrying pain (either slow or fast fibers) can cause these symptoms. Although an ischemic event precedes most central post-stroke pain, the pain can also happen after a hemorrhagic stroke, which can be either intracerebral or subarachnoid hemorrhage. Intracerebral hemorrhage can precede central post-stroke pain in the legs because of the pattern of arrangement of fibers to face, arm, trunk, and leg is mediolateral, in the ventral posterior nucleus of the thalamus. The central post-stroke pain occurs more frequently in those with acute stroke and larger lesions, but no characteristic finding on computed tomography (CT) brain scan of the patients with central post-stroke pain is identified. Brain magnetic resonance imaging (MRI) of patients with this syndrome has shown infarctions, while single-photon emission computed tomography shows decreased blood flow, especially to the left thalamus.[3][4][5]

Epidemiology

The onset of pain symptoms may vary from days to years after having a stroke. Most frequently, the symptoms start within the first six months but can develop after ten years of infarction. The prevalence of alterations in stimulus perception after stroke is variable, ranging from 11% to 85% of patients with strokes, and the prevalence of having central post-stroke pain is 8% to 46% (based on retrospective studies). Some studies have shown that central post-stroke pain is more prevalent in patients with lateral medullary syndrome (Wallenberg syndrome), and 25% of those can occur within six months. Central post-stroke pain after lateral medullary infarction may occur sub-acutely with the average period of 4 weeks (range 1 to 24 weeks). There is the difficulty in assessing the incidence of central post-stroke pain due to confounding the effect of other causes of chronic pain in patients with stroke, for example, shoulder pain, painful shoulder spasticity, primary headaches like a tension-type headache, or various musculoskeletal pains particularly affecting knees and hips. The incidence and duration of central post-stroke pain are not related to gender or age of the patient nor the side of the lesion.[6][7]

Pathophysiology

Diffusion tensor tractography (DTT) shows a 3-dimensional view and estimation of the function of the spinothalamic tract. Any lesion on the spinothalamic tract, anywhere throughout its course in the central nervous system (CNS), can cause central post-stroke pain.[8]

There are several etiologic theories proposed, which include central imbalance, central disinhibition, central sensitization, the grill illusion theory or thalamic changes, and the inflammatory response of the neural pathway involved.[9]

Central Imbalance

Central imbalance (abnormal nociception and thermal sensation) might occur due to abnormal integration between normally functioning dorsal-medial lemniscus pathway and the damaged spinothalamic tract within the multisynaptic paleo-spinothalamic pathway. Another proposed pathway of central imbalance is at the level of third level neurons of the spinothalamic pathway. Those project from the thalamus to the insular cortex or anterior cingulate region, although the mechanism is undefined.

Central Disinhibition

The ventral posterolateral nucleus of the thalamus has an intrinsic network of GABAergic neurons, which causes the intrinsic inhibition of ventral posterolateral nucleus. Stroke affecting the lateral thalamus causes central disinhibition by the deafferentation of the thalamic nucleus, which causes the activation of cortical areas resulting in pain. The slow return of neuronal function after stroke or trauma explains the timing of the pain. The disinhibition of temperature-sensing fibers (primarily those that sense cold) might be the cause of cold allodynia. 

Central Sensitization

Central sensitization is the increased synaptic efficacy of the central afferent neurons leads to spontaneous pain or nociception on suboptimal stimulus. A spontaneous bursting pattern of multifocal asynchronous electrical activity has been recorded in the deafferented thalamic nuclei, with the help of microelectrodes, in patients of central post-stroke pain. The N-methyl-D-aspartate receptor antagonists (ketamine) has helped the central pain in animal models. This provides indirect evidence for the damage of central neurons from N-methyl-D-aspartate-receptor activation in central sensitization.

History and Physical

Central post-stroke pain is a kind of hemidystonia that typically involves the areas of the body affected by stroke. This pain is a sharp, burning, and stabbing pain with the intensity of somewhere between 3 to 6 on a numeric rating scale of 0 to 10 (10 being the worst pain imaginable), along with hyperalgesia and allodynia. The patient may even complain of one or more types of pain. The quality of pain varies and is often described as pricking, aching, lancinating, shooting, squeezing, freezing, lacerating, electrical, cold, numb, swollen, cutting, dull, and throbbing. It is difficult for the patient sometimes to describe the quality of pain. Some patients describe the pain as “troublesome,” “annoying,” and “tiring.” More than 90% of patients have abnormalities in either pain or temperature sensation. In other words, modalities carried by the spinothalamic sensory tract; whereas, loss of vibration or touch sensation, in other words, modalities carried by the dorsal column-medial lemniscus pathway, is less common.

Central post-stroke pain is often split into three components. First can be a spontaneous, constant pain described as burning, aching, pricking, freezing, and squeezing. Second can be a spontaneous, intermittent component present in 15% of cases and lasting for a few seconds to minutes, intense in severity, and described as shooting and lancinating. This component may be the predominant complaint as it happens daily with pain-free intervals of a few hours. About two-thirds of the patients have a third evoked component, which is hyperalgesia, hyperesthesia, and/or allodynia. Any patient may experience one or more of these components of this neuropathic pain.

Evaluation

The diagnosis should be based on the following components:

• History (onset, location, intensity, duration, quality, aggravating factors)
• Clinical and sensory examination (to map the sensory abnormality and to rule out the other causes of pain)
• Imaging: CT/MRI brain without contrast (to confirm the history of stroke and the location and volume of lesions, if present)

Following are diagnostic criteria for central post-stroke pain is suggested by Dr. Henriette Klit, Dr. Nanna B. Finnerup and, Dr. Troels S. Jensen.

Mandatory Criteria

• Pain in an area of the body corresponding to the lesion of the central nervous system
• History suggestive of a stroke and onset of pain at or after stroke onset
• Confirmation of a central nervous system lesion through imaging or negative or positive sensory signs confined to the area of the body corresponding to the lesion
• Other causes of pain, such as nociceptive or peripheral neuropathic pain, are excluded or considered highly unlikely

Supportive Criteria

• No primary relation to movement, inflammation, or other local tissue damage
• Descriptors such as burning, painful cold, electric shocks, aching, pressing, stinging, and pins and needles, although all pain descriptors can apply
• Allodynia or dysaesthesia to touch or cold

Treatment / Management

The management of central post-stroke pain requires a multidisciplinary approach. It includes various pharmacological (antidepressants, anticonvulsants, opioids, N-methyl D-aspartate receptor antagonists, and miscellaneous therapies) and non-pharmacological options.

Dr. Henriette Klit and his coworkers propose a stepwise approach.

Antidepressants

Studies have shown that amitryptiline (75 mg) is superior to carbamazepine, according to a three-phase crossover randomized clinical trial. Amitryptiline is started from low doses of 10 to 20 mg per day, with weekly increment in dose, until the pain is relieved, and the patient has no side effects (anticholinergic effects). Pain is relieved after 4 to 7 days of reaching the optimal dose. Selective serotonin reuptake inhibitors have not been tried for central poststroke pain.

Anticonvulsants

If antidepressants are not effective, an anticonvulsant like carbamazepine is added, especially if the pain is sharp and lancinating. Carbamazepine is started with 100 mg per day (average dose 800 mg per day) with a gradual increase of dose until the pain is improved or the patient has intolerable side effects. Somnolence and dizziness are the most common side effects of carbamazepine. Gabapentin is effective for both central or peripheral origin neuropathic pain, with an optimal daily dose of 1800 mg. It is particularly effective for the spontaneous intermittent component of pain or thermal allodynia. Long-term use may cause weight gain. A single trial has shown that lamotrigine is moderately effective in central poststroke pain.

Opioids

If antidepressants and anticonvulsants are not effective alone or in combination, opioids may be considered. Intravenously-infused tramadol was found effective in patients with chronic central poststroke pain.

N-methyl D-aspartate Receptor Antagonist

Oral ketamine (maintenance dose of 50 mg three times per day) along with oral diazepam (maintenance dose of 5 mg three times per day) can be effective. Intravenous ketamine is reserved for the refractory cases of central poststroke pain.

Various Invasive and Non-Invasive Non-Pharmacological Techniques

The following are available for managing the patients but have variable efficacy.

Repetitive transcranial magnetic stimulation (r TMS): It is a motor cortex stimulation technique that is noninvasive and has a long-lasting effect.

Motor cortex stimulation: Overall results to relieve pain in the patients are variable but encouraging.

Transcutaneous electrical nerve stimulation (TENS): Especially low-frequency TENS is found to effective in combination with social support and family education.

Deep brain stimulation (DBS): It is an option of treatment in a limited number of patients. As ablation of any area of the brain might cause other deficits or even aggravates the pain.

Future of Central Poststroke Pain Management

Antiplatelet medications, especially cilostazol, may have a role in the treatment of central post-stroke pain. The thalamic hemorrhagic stroke makes cilostazol easier to pass through the blood-brain barrier due to disruption of the barrier at the site of hemorrhage. The exact mechanism of action for relieving thalamic pain is unknown.

Vestibular Caloric Stimulation (VCS): It is found to be effective, but more trials are needed.

Other modalities, such as psychotherapy, behavioral therapy, and educating patients and family about various coping strategies, are also considered. Evaluation for depression and timely management is important. patients with stroke with central post-stroke pain should be enrolled for rehabilitation and management of other co-morbidities.

Differential Diagnosis

• Cervical disk herniation
• Multiple sclerosis
• Syringomyelia
• Conversion disorder

Prognosis

Central post-stroke pain is a persistent pain and may be life-long.

Complications

• Reduces the quality of life 
• Leads to depression or anxiety
• Cause of sleep disturbance
• Prone to drug dependence 
• Poor social interactions
• Self-mutilation 
• Increases risk of suicide