Fibrinolytic therapy versus craniotomy for anticoagulant-associated intracerebral hemorrhage.

OBJECT: Anticoagulant-associated intracerebral hemorrhages (AAICH) have a high morbidity and mortality, necessitating urgent treatment. We examined outcomes after conventional craniotomy and stereotactic fibrinolytic therapy in a series of patients with anticoagulant-associated hemorrhages. METHODS: Among 129 consecutive surgically treated patients with supratentorial intracerebral hemorrhage, 27 patients with AAICH were identified (mean age 62; range 36-79). Thirteen patients underwent craniotomy for surgical hematoma evacuation, and 14 patients hematoma puncture and catheter placement for clot lysis. The groups had comparable major prognostic factors such as hematoma volume, age, and Glasgow coma scale (GCS) score at admission. RESULTS: Nine patients died despite treatment (mortality=33%). Mortality in the craniotomy group was comparable to that of the lysis group (46% versus 21%; p=0.13). Good outcomes (Glasgow outcome score of 4 or 5) were seen in 3 craniotomy patients (23%) and 2 fibrinolysis patients (14%). Half the patients survived with major neurological deficits (GOS 2 or 3) (n=13; 48%). One rebleed was observed two days after uneventful craniotomy and hematoma removal, while no patient who underwent fibrinolysis had rebleeding. CONCLUSIONS: Approximately one-fifth of patients with AAICH managed surgically may have good outcomes. Mortality and favourable outcome rates are comparable between craniotomy and fibrinolytic therapy. Fibrinolytic therapy appears to be a reasonable less invasive alternative treatment modality for intracerebral hemorrhage in the anticoagulated patient.

Decompressive craniotomy: durotomy instead of duroplasty to reduce prolonged ICP elevation.

BACKGROUND: Usually, decompressive craniectomy (DC) in patients with increased intracranial pressure (ICP) is combined with resection of the dura and large-scale duroplasty. However, duroplasty is cumbersome, lengthens operation time and requires heterologous or autologous material. In addition, the swelling brain could herniate into the duroplasty with kinking of the superficial veins at the sharp cutting edges and subsequent ICP exacerbation. Several longitudinal durotomies avoid these limitations, but it remains a matter of discussion if durotomies reduce ICP sufficiently. METHODS: DC was performed in ten patients (mean age 45 years) with increased ICP after head trauma or subarachnoid hemorrhage. After craniectomy, the dura was opened by three to four durotomies from midline to the temporal base. Duration of surgical procedure and ICP during each surgical step and postoperatively were recorded. FINDINGS: Mean duration of surgery was 90 +/- 10 min. ICP prior to skin incision was 39 +/- 12 mmHg and dropped to 22 +/- 9 mmHg after craniectomy. During durotomy ICP decreased stepwise and reached stable values of 12 +/- 6 mmHg at the end of surgery. On days 1-10 after surgery, ICP values ranged between 12-17 mmHg. CONCLUSION: This study showed that durotomy is a fast and easy, but likewise effective method to lower ICP further after craniectomy.

Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A).

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. The predominant subtype, CMT-1A, accounts for more than 50% of all cases and is associated with an interstitial chromosomal duplication of 17p12 (refs. 2,3). We have generated a model of CMT-1A by introducing extra copies of the responsible disease gene, Pmp22 (encoding the peripheral myelin protein of 22 kDa), into transgenic rats. Here, we used this model to test whether progesterone, a regulator of the myelin genes Pmp22 and myelin protein zero (Mpz) in cultured Schwann cells, can modulate the progressive neuropathy caused by moderate overexpression of Pmp22. Male transgenic rats (n = 84) were randomly assigned into three treatment groups: progesterone, progesterone antagonist (onapristone) and placebo control. Daily administration of progesterone elevated the steady-state levels of Pmp22 and Mpz mRNA in the sciatic nerve, resulting in enhanced Schwann cell pathology and a more progressive clinical neuropathy. In contrast, administration of the selective progesterone receptor antagonist reduced overexpression of Pmp22 and improved the CMT phenotype, without obvious side effects, in wild-type or transgenic rats. Taken together, these data provide proof of principle that the progesterone receptor of myelin-forming Schwann cells is a promising pharmacological target for therapy of CMT-1A.