Massimiliano Toscano

Transcranial Sonography of Basal Ganglia Calcifications in Fahr Disease

Fahr disease, also known as bilateral striopallidodentate calcinosis, is a rare degenerative neurologic disorder characterized by almost symmetric calcifications of the basal ganglia, the cerebellum dentate nuclei, the thalami, and the white matter of the cerebral hemispheres. Bilateral striopallidodentate calcinosis manifests as familial autosomal dominant but also as sporadic forms. Movement disorders (both Parkinsonism rigidity and hyperkinesia) represent the most common clinical manifestations of Fahr disease, usually followed by cognitive and cerebellar impairment.1 Neuroimaging techniques, such as cerebral computed tomography (CT) and magnetic resonance imaging (MRI), when correlated with a typical clinical history and sometimes with phosphocalcic assessment (ie, hypocalcemia and hyperphosphoremia in cases of bilateral striopallidodentate calcinosis secondary to hypoparathyroidism), are highly suggestive of bilateral striopallidodentate calcinosis: typical bilateral intracranial calcinosis can be identified. Recently, transcranial sonography has been recognized as a reliable and sensitive technique for the detection of basal ganglia abnormalities in several movement disorders, such as Parkinsonism, corticobasal degeneration, Wilson disease, and other extrapyramidal disorders.2–4 To our knowledge, no cases of basal ganglia alterations in Fahr syndrome as shown with this technology have been reported previously. A 54-year-old man was admitted to our neurologic ward for a sudden worsening of extrapyramidal symptoms with gait freezing and postural instability. His clinical history started several years before, and he was receiving L3,4-dihydroxyphenylalanine treatment. Cerebral MRI at admission showed extensive calcifications involving the basal ganglia, dentate nuclei, and cerebellar hemispheres, supporting Fahr syndrome (Figure 1). Transcranial sonography was performed through the temporal acoustic bone windows using a phased array ultrasound system equipped with a 2-MHz transducer (S2000; Siemens AG, Erlangen, Germany). The sonographic parameters were set according to previous criteria indicated in the literature1,2: the insonation depth was set at 13 cm to the visualization of the opposite temporal bone; the dynamic range of the images was set at 50 dB; persistence was set on high; and reject was set on 7. The image brightness and time gain compensation were adjusted to the best contrast. The brain stem, basal ganglia, and ventricles were investigated on standardized axial transcranial sonographic scanning planes.5 We observed increased echogenicity in the substantia nigra in the mesencephalon (Figure 1A), diencephalon (Figure 1B), thalamus (Figure 1C), and lateral ventricles (Figure 1D). All of these findings corresponded to MRI abnormalities (Figure 1, right panels). Neuroimaging techniques play a pivotal role in the diagnosis of bilateral striopallidodentate calcinosis because both CT and MRI are able to show intracranial calcifications.6 To date, CT remains the most effective screening tool in defining the site and extent of the calcifications, but false-negative results may still arise because the minimum age at which negative CT findings exclude the disease in not established.7 Magnetic resonance imaging seems to be more sensitive in depicting the various stages of the disease because low–signal intensity areas on T2-weighted spin echo sequences reflect an early stage of calcium deposition, whereas high-signal intensity areas probably reflect a later stage of calcinosis, with increased proteins and endothelial membrane incompetence.6 Nonetheless, a potential limit of MRI for Fahr disease is that images of calcifications may show different signal intensities, thus confounding its differential diagnosis. Transcranial sonography is a very diffuse, relatively low-cost, noninvasive imaging technique that finds application not only in cerebrovascular diseases but also in several other neurologic conditions, such as brain parenchymal imaging in movement disorders, when the temporal bone window is adequate for the investigation. Transcranial sonography can indeed reveal basal ganglia degeneration and altered echogenicity of the substantia nigra even in early Parkinson disease2,3 but also in other degenerative disorders such as Wilson disease.4 To our knowledge, a well-documented report of transcranial sonography in Fahr disease in which calcifications of the basal ganglia (which cause hyperechogenicity on sonography) could be easily identified has not been published previously. This case further confirms the utility of transcranial sonography in the evaluation of brain parenchymal changes in movement disorders.

Noninvasive imaging of carotid arteries in stroke: emerging value of real-time high-resolution sonography in carotid occlusion due to cardiac embolism.

Objective. Comprehension of the pathophysiologic characteristics of atherosclerosis has focused its attention on the study of dynamic and metabolic processes involving the vessel wall as possible causes of stroke. When compared with conventional radiologic techniques, sonography has the main advantage of being a real‐time imaging modality. We report 2 acute stroke cases in which carotid sonography showed some dynamic features that could not be identified with computed tomography (CT) and magnetic resonance angiography (MRA). Methods. Carotid sonography with high‐resolution probes (9–14 MHz) was compared with CT and MRA findings showing carotid axis occlusion in 2 patients with acute stroke. Results. In case 1, the internal carotid artery occlusion observed on CT and MRA was interpreted as a dissection on a clinical basis, but sonography showed a mobile embolus originating from the heart in the internal carotid artery. In case 2, the occlusion of the whole carotid axis observed on CT and MRA was instead related to a heart‐originating embolus floating in the common carotid artery. Conclusions. The evaluation of dynamic aspects of atherosclerosis is fundamental to understanding the pathophysiologic characteristics of stroke. Sonography is fundamental in carotid artery imaging for its possibility of showing dynamic processes that could be misdiagnosed with “static” imaging. The correct identification of the pathophysiologic characteristics of stroke in these cases could have led to different diagnostic and therapeutic algorithms.

Lack of habituation of evoked visual potentials in analytic information processing style: evidence in healthy subjects

Habituation is considered one of the most basic mechanisms of learning. Habituation deficit to several sensory stimulations has been defined as a trait of migraine brain and also observed in other disorders. On the other hand, analytic information processing style is characterized by the habit of continually evaluating stimuli and it has been associated with migraine. We investigated a possible correlation between lack of habituation of evoked visual potentials and analytic cognitive style in healthy subjects. According to Sternberg–Wagner self-assessment inventory, 15 healthy volunteers (HV) with high analytic score and 15 HV with high global score were recruited. Both groups underwent visual evoked potentials recordings after psychological evaluation. We observed significant lack of habituation in analytical individuals compared to global group. In conclusion, a reduced habituation of visual evoked potentials has been observed in analytic subjects. Our results suggest that further research should be undertaken regarding the relationship between analytic cognitive style and lack of habituation in both physiological and pathophysiological conditions.

Serotonergic Correlation with Anger and Aggressive Behavior in Acute Stroke Patients: An Intensity Dependence of Auditory Evoked Potentials (IDAP) Study

Anger and aggressive behavior (AB) are two of the main post-stroke behavioral manifestations, which could imply both an anger trait (TA) or a state condition of anger (SA). Serotonergic system is thought to play an inhibitory control on aggressive impulse. Nevertheless, whether 5HT has the same role in TA and in SA, is still debated. Intensity dependence of auditory evoked potentials (IDAP) is thought to be inversely related to the central 5HT tone. The aim of this study was to evaluate, in acute stroke patients, the 5HT system involvement in AB by IDAP. Consecutive stroke patients were evaluated and compared with healthy controls. The Spielberger Trait Anger Scale (STAS) was used to assess AB, SA and TA. Patients with AB and TA showed a significantly increased IDAP value, whereas patients with SA had a significantly lower IDAP; this indicates an increased 5HT tone. In acute stroke patients with AB, there is a decreased central 5HT tone. Surprisingly, we found an opposite 5HT feature between patients with TA and those showing SA, suggesting that the hypothesis of aggression based on 5HT deficiency requires further investigations. This might open new strategies in the treatment of post-stroke AB.

Acute subcortical stroke and early serotonergic modification: a IDAP study

The intensity dependence of the auditory‐evoked potentials (IDAP) is inversely related to serotonergic tone. Depression is frequently observed after stroke, associated with cognitive impairment and increased mortality. Aim of this study was to investigate the serotonergic tone in acute stroke patients by IDAP. Consecutive patients with an acute stroke admitted in our stroke unit were evaluated using clinical and instrumental examinations and compared with healthy controls. The IDAP was calculated as the linear amplitude/stimulus intensity function (ASF) slope, by measuring the peak‐to‐peak amplitude of Nl‐P2 on four blocks of different stimulus intensities. Twenty patients were enrolled; 11 had a right brain infarction; nine had depressive symptoms (DS). The ASF slope of the auditory‐evoked potentials was markedly increased in stroke patients compared with controls (P = 0.021). Stroke patients with DS had a significant steeper ASF slope than controls (P = 0.017). There was no statistical difference in ASF slope between stroke patients without DS and controls. Post‐stroke depression pathophysiology is still debated. Our study suggests that in acute stroke patients with DS, there is a direct involvement of the serotonergic system, regardless the degree of disability and the site of the lesion.

Optic Nerve Sheath Diameter Ultrasound Evaluation in Intensive Care Unit: Possible Role and Clinical Aspects in Neurological Critical Patients’ Daily Monitoring

Background. The increase of the optic nerve sheath diameter (ONSD) is a reliable, noninvasive sonographic marker of intracranial hypertension. Aim of the study was to demonstrate the efficacy of ONSD evaluation, when monitoring neurocritical patients, to early identify malignant intracranial hypertension in patients with brain death (BD). Methods. Data from ultrasound ONSD evaluation have been retrospectively analyzed in 21 sedated critical patients with neurological diseases who, during their clinical course, developed BD. 31 nonneurological controls were used for standard ONSD reference. Results. Patients with neurological diseases, before BD, showed higher ONSD values than control group (CTRL: RT 0.45 ± 0.03 cm; LT 0.45 ± 0.02 cm; pre-BD: RT 0.54 ± 0.02 cm; LT 0.55 ± 0.02 cm; p < 0.000) even without intracranial hypertension, evaluated with invasive monitoring. ONSD was further significantly markedly increased in respect to the pre-BD evaluation in neurocritical patients after BD, with mean values above 0.7 cm (RT 0.7 ± 0.02 cm; LT 0.71 ± 0.02 cm; p < 0.000), with a corresponding dramatic raise in intracranial pressure. Logistic regression analysis showed a strong correlation between ONSD and ICP (R 0,895, p < 0.001). Conclusions. ONSD is a reliable marker of intracranial hypertension, easy to be performed with a minimal training. Routine ONSD daily monitoring could be of help in Intensive Care Units when invasive intracranial pressure monitoring is not available, to early recognize intracranial hypertension and to suspect BD in neurocritical patients.

Hemodynamic Features of Non-Aneurysmal Subarachnoid Hemorrhage in a Case of Familial Moyamoya Disease: A Transcranial Doppler Ultrasound Study

Willis circle with absence of the ACAs and of L-MCA and multiple tortuous vessels branching from the R-MCA (‘moyamoya vessels’). No aneurysms or vascular malformations were found ( fig. 1 ). Based on these findings, the patient was diagnosed with MMD. No neurological deficits were noted on the patient’s physical examination. Upon admission, we performed a Carotid Duplex ultrasound and a TCD, which showed an increase in mean blood flow velocity of R-MCA. This was initially attributed to vasospasm and nimodipine therapy was started. We also performed a progressive TCD follow-up; hemodynamic parameters of the first ultrasound examination as well as those from TCD follow-up are summarized in table 1 (we exclusively reported follow-up values from the R-MCA, which were the only ones that showed significant changes through time). The patient had a very favorable outcome and is currently asymptomatic. Particularly interesting is the monitoring of hemodynamic state of brain vessels done in our case. According to previous studies performed on asymptomatic MMD patients [6] , we found at T0 that both the ICAs showed normal flow velocity and low resistance, while the remaining intracranial vessels showed a consistent hemodynamic pattern in terms of high flow velocity and low resistance. This pattern re

Cardioembolic stroke: Protective effect of a severe internal carotid artery stenosis in a patient with cardiac embolism.

Cardioembolic stroke is generally caused by intracranial artery occlusion. Clots may be identified in the intracranial vessels by means of conventional neuroimaging in the acute phase. High‐resolution ultrasonography may show some features suggestive of cardiac emboli when occluding extracranial carotid arteries. We describe a patient with cardioembolic ischemic stroke in the right hemisphere in whom a left internal carotid artery stenosis paradoxically protected the ipsilateral hemisphere from distal intracranial embolism. The patient also presented multiple acute ischemic embolic lesions in the right middle cerebral artery territory and in the right occipital lobe, which was fed by the posterior cerebral artery, anomally originating from the right carotid siphon. Interestingly, the left internal carotid artery—which showed a severe preexisting stenosis—was occluded by the cardiac clot, whereas the right internal carotid artery only presented a moderate stenosis that had probably allowed the clots to pass. Therefore, the severe left internal carotid artery stenosis may have blocked the cardiac embolus, preventing it from reaching the ipsilateral hemisphere.

Predictors and Timing of Recanalization in Intracranial Carotid Artery and Siphon Dissection: An Ultrasound Follow-up Study

Background: Intra- and extracranial internal carotid artery dissections (ICD) are two different pathological conditions. Extracranial dissection is considered to be among the most frequent causes of stroke in the young and the segment generally reopens in 2 out of 3 cases, completely or partially, within 6 months. Intracranial ICD (IICD) is considered a rare occurrence in stroke and, accordingly, there are few systematic published data. However, it is a clinically significant condition that may cause severely disabling ischemic stroke or subarachnoid hemorrhage. In the past, sole availability of invasive imaging methods for its detection may have induced an underreporting. The aim of the study was to analyze ultrasound findings, timing and predictors of recanalization in patients with IICD. Methods: IICD acute patients admitted to our Stroke Unit were submitted to carotid sonographic seriated monitoring, daily for the 1st week after symptom onset, at day 14, at month 1 and every 3 months thereafter up to a follow-up of 4 years. Contrast carotid ultrasound was performed in patients with persistent occlusion after month 1. Results: Fourteen acute patients with IICD were enrolled. Extracranial internal carotid patency was observed in 8 patients at first ultrasound scans; all of these showed complete intracranial recanalization within the 1st week and oral anticoagulants were withdrawn after 6 months. Conversely, in 6 patients retrograde extracranial internal carotid thrombosis was immediately observed, since the first ultrasound scans. In 4 of these the occlusion persisted after 4 years while 2 of them had only a partial recanalization, with evidence at contrast ultrasound of still late remodeling processes in the extracranial thrombus up to 2 years after the first observation; for this reason, in these 2 patients anticoagulation was not discontinued, while in the 4 patients with persistent, stable, occlusion, therapy was suspended 1 year after the diagnosis. Conclusions: Identification of the site of dissection - i.e. extra- versus intracranial - is fundamental in clinical studies for outcome and prognosis evaluation. Carotid ultrasound strict surveillance is important to monitor eventual recanalization in patients with ICD, even in a late phase. Retrograde internal carotid thrombosis seems to be correlated with persistent occlusion and partial recanalization. Remodeling of thrombotic material in the internal carotid artery may, however, continue for up to 2 years. In these cases, contrast ultrasound evidence of thrombus morphological changes may support the decision to continue anticoagulation.

Letter by Toscano et al Regarding Article, "Association of Leukoaraiosis With Convalescent Rehabilitation Outcome in Patients With Ischemic Stroke".

We read with great interest the article by Senda et al1 about the association between leukoaraiosis and inpatient rehabilitation outcome after an ischemic stroke. To investigate the factors influencing convalescent rehabilitation outcome, Senda et al1 analyzed the burden of the leukoaraiosis for each single stroke subtypes, according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Hence, they evaluated the impact of the type of white matter damage on recovery. This showed that periventricular hyperintensity influenced motor function recovery, whereas deep white matter hyperintensity influenced cognitive …