Any headache in the course of Lyme disease could be an early manifestation of invasion of the CNS by spirochaetes. The most characteristic symptoms of early neuroborreliosis are meningitis with cranial or peripheral neuropathies connected with radiculopathies, less common are encephalitis and myelitis, neuropathies, polyneuropathies, encephalopathies. Encephalomyelitis is the most serious form of neuroborreliosis. From the pathophysiologic point of view all cranial and peripheral neuropathies are forms of mononeuritis multiplex. Encephalopathy is due to neuroimmunomodulators, like lymphokins and or by toxico-metabolic effect could be connected with each form of systemic borreliosis. Certain diagnosis of neuroborreliosis is based on culturing of B. burgdorferi from CSF, detection of specific antispirochaetal antibodies produced in the subarachnoid space, detection of activated lymphocytes B producing specific antibodies, detection in CSF of other antigens of B. burgdorferi or DNA sequences.